Dear Editor, Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterize... more Dear Editor, Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of histiocytes exhibiting emperipolesis and with an immunophenotype characterized by positivity for S-100 and CD68, and negativity for CD1a and langerin. The classic pattern of the disease primarily presents with painless and bilateral cervical lymphadenopathies accompanied by fever, leukocytosis, an increased sedimentation rate, and polyclonal hypergammaglobulinemia. Approximately 40% of RDD patients exhibit extranodal involvement. The skin is involved in 10% of extranodal RDD cases. Lesions are typically characterized by slow growing, painless, non-pruritic nodules, plaques, or papules with coloration varying from yellow to red to brown. A 70-year-old man was admitted due to enlarged lymph nodes and painless cutaneous lesions starting on the face and subsequently extending to the neck and trunk over a 3-year period. The patient had a history of polypoid lesion excision from the paranasal sinuses due to nasal obstruction 6 months previously. Dermatological examination revealed yellow-spotted red-colored indurated papulonodular lesions, plaques and nodules up to 4 cm in diameter, particularly on the face, neck, back, and trunk (Figure 1A-C). Dermatoscopic examination
In conclusion, three interesting results were identified after analysis of data in our study. Fir... more In conclusion, three interesting results were identified after analysis of data in our study. First, our overall mortality rate was 1 in 19 (5.3%). Higher mortality rates were reported in previous studies (10%-20%) [1,2]. This result may show that early PEX initiation is an effective factor in mortality reduction. Secondly, the mean d-dimer value of our TTP patients was higher than the reference limit at 2.65 µg/mL (reference values: 0-0.4 µg/mL). Thus, in cases of slightly elevated d-dimer levels, one should not hesitate to start urgent PEX treatment in patients with clinically high suspicion of TTP if ADAMTS13 panel results are not obtained quickly. Thirdly, relapsed/refractory patients needed more PEX sessions to achieve first remission. A smaller number of PEX sessions to achieve response may be predictive of durable remission without relapse.
Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Alt... more Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion. Since CTNNB1 (β-catenin gene) exon 3 mutations were frequently detected in some rare fibrovascular lesions, we aimed to investigate the presence of oncogenic CTNNB1 mutations in SANT cases. For this purpose, 7 cases of SANT with typical histopathological features were retrieved. First, the presence of CTNNB1 exon 3 alterations was examined with a recently described immunohistochemistry-based method. Then, the findings were confirmed with polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), and Sanger sequencing. In all cases, immunochemistry of β-catenin gave a staining pattern that was suggestive of exon 3 alteration; however, no missense mutations were found in any case at the CTNNB1 exon 3 hotspot region. Subsequently, we screened for large interstitial deletions of CTNNB1 exon 3 which revealed short PCR products in three cases. Sequencing confirmed that these cases had large interstitial deletions, resulting in loss of the entire exon 3 of CTNNB1 . In the remaining four cases, loss of exon 3 was documented at the cDNA level, although genomic deletion was not identified. These results demonstrate that loss of CTNNB1 exon 3 and stabilization of β-catenin with activation of Wnt signaling pathway might have a significant role in the pathogenesis of SANT. Through this study, we provided important evidence for the neoplastic nature and pathogenesis of this disorder.
Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic li... more Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic lifelong disease, which could be manageable with tyrosine kinase inhibitor (TKI) drugs. The aim of TKI drug treatment is to provide age-and sex-matched duration of life in a given patient with CML. Personalized CML treatment with TKI drugs is the key strategy. Individual treatment approach includes the harmonization of CML disease characteristics, clinical experience, and best available clinical evidence. Specific CML disease characteristics in a given patient include; CML disease risk, comorbidities, molecular profile, compliance, lifestyle, and drug off-target risk profile. CML research evidence includes; randomized clinical trials indicating the data on the efficacy, safety, tolerability, toxicity, possible longterm adverse events, and pharmacoeconomy of TKIs. Clinical and physician experience includes TKI availability, TKI reimbursability, drug experience, adherence, and BCR-ABL1 monitorization facilities. The key decision of choosing a TKI of choosing TKIs for CML should be made via the consideration of these variables. The aim of this paper is to outline the latest 2016 World Health Organization definition of CML and its proper management with TKI-class drugs.
Introduction: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma with dist... more Introduction: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma with distinguishes clinical, biologic, and molecular characteristics. The MCL-International Prognostic Index (MIPI) incorporates age, EGOC performance status, normalized LDH level and WBC and has improved discriminatory power. The aim of this retrospective single-center study was to evaluate the clinical characteristics and response to treatment of patients with mantle cell lymphoma. Methods: This single center retrospective study included 297 adult patients diagnosed with MCL between December 2005 and May 2018. The diagnosis of MCL was rendered in accordance with the later World Health Organization (WHO) classification. Outcome was determined as response to treatment, progression free survival (PFS) and overall survival (OS) by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. We also compared the PFS and OS according to simplified MIPI (s-MI...
Retrospektif ozellikteki calismamiza 1996-2001 yillari arasinda bolumumuzde KML tanisi almis ve A... more Retrospektif ozellikteki calismamiza 1996-2001 yillari arasinda bolumumuzde KML tanisi almis ve Ankara Univeristesi Tip Fakultesi Hematoloji Bilim Dali Kemik iligi Transplantasyon Unitesinde kemik iligi nakli olmus 24 hastaya ait toplam 58 adet kemik iligi biyopsisi dahil edilmistir. Hastalara ait tani, nakil oncesi ve nakil sonrasi kemik iligi biyopsi, imprint ve kemik iligi aspirasyon materyalleri yeniden degerlendirilmistir. Calismada evreleme amaciyla orneklenen, tutulum bulundurmayan normoselluler 17 adet kemik iligi biyopsisi kontrol grubu olarak degerlendirmeye alinmistir. Kemik iligi biyopsi, imprint ve aspirasyon preparatlarinda KML fazi WHO-2001 kriterlerine gore belirlenmistir. H&E kesitlerde kemik iligi sellularitesi belirlenmistir. Biyopsilere retikulin derecelendirmesinin yapilabilmesi icin histokimya ile retikulin ve gerekli hastalarda trikrom boyalari, anjiogenezin degerlendirilebilmesi icin immunhistokimya ile anti-FVIII-RA boyalari uygulanmistir. Retikulin derecelendirmesi Bauermeister'in tanimladigi kantitatif kemik iligi retikulin degerlendirme semasi esliginde degerlendirilmistir. Anjiogenezin degerlendirmesinde ise, anti-FVIII-RA boyali preparatlarda morfometrik olarak, goruntu analiz sisteminde (Image Analysis System, Carl-Zeiss Vision GmbH, Hallbergmoas, Germany) KS-400 goruntuleme programi (Imaging System) ile damar alani, damar alaninin degerlendirmenin yapildigi alana orani ve damar sayisi olcumleri yapilmistir. Ayrica morfometrik olcumlerin yapildigi alanlarda alan sellularitesi ve megakaryosit sayisi belirlenmistir. Hasta ve kontrol biyopsilerinde hastalarin cinsiyeti, yasi, hastalarda tani, nakil oncesi, nakil sonrasi biyopsi ve kemik iligi nakil tarihleri belirlenmistir. Hastalarda kullanilan konvansiyonel tedavi protokolleri ve klinik bilgilerine ulasilmistir. KML hastalarinda yas, cinsiyet dagilimi literaturle uyumlu bulunmustur. KML gelisen hastalarda hastaliksiz kisilere gore kemik iligi genel ve alan sellularitesi, megakaryosit sayisi, damar alani ve damar alan oraninda ve retikulin derecelerinde artisin oldugu saptanmistir. Damar sayisinda ise nakil oncesi ve sonrasi degerlerde kontrol degerlerine gore yuksek sonuclar elde edilmistir. KML hastalarinda kullanilan konvansiyonel tedavi protokollerinin kemik iligi sellularitesi, damar sayisi, damar alani, damar alan orani, megakaryosit sayisi ve retikulin derecesine etkisinin olmadigi gorulmustur. Yanlizca nakil oncesi biyopsilerde hidroksiure-interferon- tedavisinin damar sayisinda artisi ile iliskili oldugu bulunmustur. Kemik iligi naklinden (KIT) sonra genel ve alan sellularitesi, retikulin derecesi ve megakaryosit sayisinin azaldigi saptanmis, bu parametrelerin KIT'den sonra kontrol grubuna yakin degerlere ulastigi tespit edilmistir. Bu sonuclar KIT'in KML hastaligini tam olarak tedavisini sagladiginin gostergesidir. Ancak vaskuler parametreler olan damar sayisi, damar alani ve damar alan oranlarinda KIT sonrasinda degisiklik gozlenmemistir. Bu sonucta KIT sonrasi erken donemde engrafman ve aktif proliferasyonun vaskuler parametrelerin yuksek bulunmasinda rol oynayabilecegini, bu nedenle kesin degerlendirme yapabilmek icin daha gec donem biyopsilerin de degerlendirilmesinin gerekliligini dusundurmektedir. Vaskuler parametreler olarak degerlendirmesi yapilan damar sayisi, damar alani ve damar alan orani degerlerinde tespit edilen artista retikulin dererecesi, megakaryosit sayisi, genel ve alan sellularitesi, hasta yasinin etkisinin olmadigi bulunmustur. Calismamizda farkli vaskuler parametreler anjiogenezin degerlendirmesinde kullanilmistir. Bu parametrelerin kendi aralarinda ve anjiogenezle iliskili oldugu bilinen diger parametrelerle yapilan karsilastirmalarinda tek basina damar sayisinin ele alinmasinin saglikli ve guvenilir bir yontem olmayabilecegi, anjiogenezin guvenilir olarak degerlendirilebilmesi icin morfometrik olarak damar alani, damar alan oran olcumlerinin damar sayimi ile birlikte kullaniminin daha anlamli olacagi sonucuna ulasilmistir. Anjiogenezin degerlendirilmesinde elde edilen bu sonuclar ile KML hastalarinda kemik iliginde anjiogenezin hastalikla birlikte belirgin artmis bulunmasinin konvansiyonel tedaviye yardimci olarak antianjiogenetik ilaclarin kullaniminin faydali olabilecegini dusundurmustur. Bunun kesin olarak gosterilebilmesi icin prospektif, genis hasta gruplarini iceren calismalara ihtiyac bulunmaktadir.
Aims: To determine the distribution of factor VIII related antigen, CD31, CD34 and CD36 in normal... more Aims: To determine the distribution of factor VIII related antigen, CD31, CD34 and CD36 in normal and malignant human vascular tissues using a panel of well characterised monoclonal antibodies.
Indian Journal of Hematology and Blood Transfusion, 2020
Purpose Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hemato... more Purpose Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hematological malignancy. There is still no standard treatment established for BPDCN patients. We aim to summarize the main clinical, biological features and treatment of 9 BPDCN patients. Methods Nine patients with BPDCN who had been diagnosed between July 2008 and December 2018 in Ankara University School of Medicine, were retrospectively evaluated. Results All patients (n = 9) were male, median age was 64 (21–80). Five patients (55.6%) had bone marrow infiltration, 5 patients (55.6%) cutaneous lesions, 6 patients (66.7%) lymph node involvement, 2 patients (22.2%) central nervous system involvement and 2 patients (22.2%) spleen involvement at time of diagnosis. Complex karyotype was observed in 2 patients. CHOP was given to 5 patients (55.6%), hyper-CVAD to 2 patients (22.2%), fludarabine, cyclophosphamide and mitoxantrone to 1 patient (11.1%) and cyclophosphamide, etoposide, methylprednisol...
Dear Editor, Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal ... more Dear Editor, Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal proliferation of histiocytes and skin manifestations are variable. Diffuse neonatal hemangiomatosis (DNH) has been described in patients with congenital self-healing reticulohistiocytosis (CSHR) and in very few cases of multisystemic LCH. Here, we present a rare case of LCH mimicking DNH and seborrheic dermatitis with multisystemic involvement. A 4-month-old female infant presented to our department with widespread erythematous and yellow scaly rash, accompanied by an intermittent fever for 2 months. These erythematous lesions first began on the inguinal region and disseminated all over the body. On physical examination, multiple discrete red-purple papules and white macules ranging in size from 0.3 to 0.8 cm, located mainly on the trunk and extremities, were identified. She had also orange-yellow scaly and crusted papules on the head and neck (Figure 1). Dermatoscopy revealed red struct...
Background: Recently Bergsagel et al have published a hierarchical model of myeloma evolution bas... more Background: Recently Bergsagel et al have published a hierarchical model of myeloma evolution based on cytogenetics and Cyclin (Cy) profiles. Previously we had reported flow cytometric expression profiles of these Cy and CDKI’s in unsorted marrow samples (Blood98 (11): 4230,2001) but had not been able to detect the parallelism between Cy-CDKI’s which we observed in the normals in the myeloma patients. Aim: Here in this study we aimed to analyze the same Cy and CDKI’s in marrow plasma cells by multiparameter immunocytochemistry and to evaluate the association with clinical parameters and impact on survival. Patients and methods: Fourty five myeloma patients diagnosed in our department between 1998–2004, aged 57(33–79), M/F:29/16 whose bone marrow biopsy specimens could be retrieved were included in the analysis. All patients were treated with VAD or MP as first line treatment. Staining was performed using monoclonal antibodies: Cyclins A, D1, p16, p21 (LabVision), Cy D3(DAKO) and Cy ...
Introduction: Several studies have attempted to describe the characteristics associated with larg... more Introduction: Several studies have attempted to describe the characteristics associated with large granular lymphocytosis (LGL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its clinical significance. However the clinical features of LGL lymphocytosis in the allo-HSCT setting is still sparse. The current study represents a detailed review of 667 patients transplanted in a single center with the objective to define the incidence of LGL lymphocytosis, to identify associations with transplant-related clinical parameters and to assess the impact on transplant related outcomes. Patients and Methods: During a 14-year follow up period (2005-2017) in this unicentric cohort study, we identified 19 patients (2.8%) with a significant LGL lymphocytosis, among 667 consecutive adult patients who underwent allo-HSCT. LGL lymphocytosis was defined as the presence of at least two of the following criteria: (1) sustained lymphocytosis above 3.0x109/L observed in at leas...
The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fou... more The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fourth edition of WHO classification of tumors of endocrine organs and the fourth edition of WHO classification of tumors of hematopoietic and lymphoid tissues are recently published. The updates in both fields include some new disease descriptions and prognostic markers. Our aim in this review article is to give practical diagnostic information about the most frequently seen hematolymphoid involvements of the pituitary gland, thyroid, and adrenal tissue. We designed the text in the order of organs and the contents according to the disease frequency. The pituitary gland and cellar region are the most frequently involved with Langerhans cell histiocytosis. Although it is very rare, Erdheim-Chester disease has recently been included in the classification and still needs more clear diagnostic definitions. Lymphoproliferative thyroid lesions and presentations create diagnostic problems for the ...
Virchows Archiv : an international journal of pathology, Jan 9, 2017
Our aim in this study was to describe the clinical, morphological, and molecular profile of gastr... more Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years...
Çok az sayıda izole kemik tutulumu ile ortaya çıkan saçlı hücreli lösemi olgusu bildirilmiştir. B... more Çok az sayıda izole kemik tutulumu ile ortaya çıkan saçlı hücreli lösemi olgusu bildirilmiştir. Biz burada izole kemik lezyonları olan bir saçlı hücreli lösemi olgusunu bildiriyoruz. Hastanemize 48 yaşında bir erkek 3 yıldır olan sol diz ağrısı ile başvurdu. Hastanın önceki şikayetleri sırasında manyetik rezonans görüntüleme yapılmış olup herhangi bir patolojik bulguya rastlanmamıştı. Direkt röntgen incelemede tibiada kistik infiltratif bir lezyon gözlendi. Hastanın bilgisayarlı tomografi görüntülemesi ılımlı splenomegali dışında normaldi. Tüm vücut pozitron emisyon tomografisinde kemiklerde çok sayıda patolojik tutulum mevcuttu. Kemik iliği biyopsisi ve aspirasyonun morfolojisi ile akım sitometrisi herhangi bir tutulum olmaksızın normaldi. Bunun üzerine tibiadaki lezyondan kemik biyopsisi yapıldı. Yapılan kemik biyopsisinin morfolojisi tipik saçlı hücreli lösemi ile uyumluydu. İmmünhistokimya sonuçlarında güçlü CD20, CD25, anneksin A1; soluk siklin D1 pozitifliği ve %5'ten daha az Ki 67 proliferasyon indeksi saptandı. Sanger sekans yöntemiyle yapılan moleküler analizde saçlı hücreli lösemi tanısını destekleyen BRAF V600E mutasyonu gözlendi. Hasta 7 gün 0.1 mg/kg kladribin ve ek lokal radyoterapi aldı. Hasta 3 yıl sonra hala remisyonda olup ilerleyici lezyonları bulunmamaktadır. Sonuç olarak, saçlı hücreli lösemi hastalarında nadir bir ortaya çıkış şekli olan izole kemik tutulumuna tanısal araç olarak BRAF V600E mutasyonuna dikkat çekmek istiyoruz.
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (D... more As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil,
Addressing the global burden of cancer, understanding its diverse biology, and promoting appropri... more Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the World Health Organisation, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UNdefined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterised by a validated prognostic gene expression score (p<0.0001), but International Prognostic Index-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.
Bu calismada patoloji arsiv materyalinden elde edilen DNA ornekleri ile yeni nesil dizileme tekno... more Bu calismada patoloji arsiv materyalinden elde edilen DNA ornekleri ile yeni nesil dizileme teknolojileri kullanilarak JAK2 ekzon 12 ve ekzon 14 (JAK2V617F) ve MPL ekzon 10 (MPLW515L, MPLW515K, MPLA506T ve MPLA519T) mutasyonlarinin arastirilmasi ve patoloji arsiv materyallerinde mutasyonlu hucre orani hastalik prezentasyonu iliskisinin tespitinde yeni nesil dizileme teknolojilerinin duyarliligi arastirilmistir.Ankara Universitesi Tip Fakultesi Patoloji Anabilim Dali’da 2001-2011 yillari arasinda kemik iligi biyopsi ve yayma preparatlari incelenen BCR ABL negatif MPN (ET, PV, PMF) tanisi almis hastalar calismaya alinmistir. JAK2 ve MPL mutasyonlarini saptamak amaciyla yeni nesil dizileme (pirosekanslama) yontemi kullanilarak molekuler analiz gerceklestirilmistir.Yas, cinsiyet dagilimlari ile laboratuvar bulgulari hastaliklarin evreleriyle beklenen sinirlar iceriside bulunan serimizde tum olgularin % 66.6’inde JAK2 ekzon 14 V617F mutasyonu bulundugu ve % 33.4 olgunun yabanil tip oldugu saptanmistir. JAK2 ekzon 12 mutasyonu ve MPL ekzon 10 mutasyonu ise sadece iki ayri ET tanili olguda (% 1.75) saptanmistir. ET (% 69.6) ve PMF (% 55.6) tani gruplarinda JAK2V617F mutasyonu klasik kaynaklarda bildirildiginden daha yuksek oranda, PV (% 75) olgularinda ise daha dusuk oranda bulunmustur. JAK2V617F-pozitif klonunun buyuklugu anlaminda olan “Allel burden” orani en dusuk PMF olgularinda, bunu izleyen oranda ET ve en yuksek PV olgularinda bulunmustur. Sellularite ve kan lokosit duzeyleri ile allel burden orani arasinda anlamli iliski saptanmistir. Bu calismada kemik iligindeki tum farkli klonlari iceren materyallerde, yeni nesil dizileme teknolojisinin metot olarak tercih edilmesindeki en onemli avantajlarindan biri olan allel burden durumunuun yuksek hassasiyet ile tespit edilebildigi gorulmustur.AbstractIn this study, we aimed to investigate JAK2 exon 12 and JAK2 exon 14 (JAK2V617F) mutations and MPLW515L, MPLW515K, MPLA506T and MPLA519T mutations, on DNA extracted from pathology archieve materials using Next Generation Sequencing Technologies. Also we aimed to evaluate the relationship between disease presentation and the“allele burden” ratios by this molecular analysis on bone marrow samples.The bone marrow biopsies and smears diagnosed as BCR ABL negative MPN (ET, PV, PMF) between 2001-2011 in Ankara University Faculty of Medicine Department of Pathology were selected for the study. The molecular analysis by using Next Generation Sequencing (pyrosequencing) was performed for detection of JAK2 and MPL mutations.Our series showed compatible age, gender and laboratory findings with the stages of the diasease groups. JAK2 exon 14 V617F mutation was examined in %66.6 of the patients. JAK2 exon 12 mutation and MPL exon 10 mutation was examined only on two distinct ET case (%1.75). The diagnostic groups ET (%69.6) and PMF (%55.6) in our series were presenting higher JAK2V617F mutation compared to the classical literature. In the PV (%75) group the mutation ratio was lower than the classical literature. “Allel burden” which represents the amound of JAK2V617F mutated clone ratio was lowest among PMF cases, followed by ET. The ratio was highest among PV cases. A positive relation between cellularity, blood leokocyte levels and allel burden was examined. We determined that performing the next generation sequencing method for the bone marrow samples which contain all of the different clones, has the advantage of giving information on detection of allel burden status with high sensitivity.
Dear Editor, Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterize... more Dear Editor, Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of histiocytes exhibiting emperipolesis and with an immunophenotype characterized by positivity for S-100 and CD68, and negativity for CD1a and langerin. The classic pattern of the disease primarily presents with painless and bilateral cervical lymphadenopathies accompanied by fever, leukocytosis, an increased sedimentation rate, and polyclonal hypergammaglobulinemia. Approximately 40% of RDD patients exhibit extranodal involvement. The skin is involved in 10% of extranodal RDD cases. Lesions are typically characterized by slow growing, painless, non-pruritic nodules, plaques, or papules with coloration varying from yellow to red to brown. A 70-year-old man was admitted due to enlarged lymph nodes and painless cutaneous lesions starting on the face and subsequently extending to the neck and trunk over a 3-year period. The patient had a history of polypoid lesion excision from the paranasal sinuses due to nasal obstruction 6 months previously. Dermatological examination revealed yellow-spotted red-colored indurated papulonodular lesions, plaques and nodules up to 4 cm in diameter, particularly on the face, neck, back, and trunk (Figure 1A-C). Dermatoscopic examination
In conclusion, three interesting results were identified after analysis of data in our study. Fir... more In conclusion, three interesting results were identified after analysis of data in our study. First, our overall mortality rate was 1 in 19 (5.3%). Higher mortality rates were reported in previous studies (10%-20%) [1,2]. This result may show that early PEX initiation is an effective factor in mortality reduction. Secondly, the mean d-dimer value of our TTP patients was higher than the reference limit at 2.65 µg/mL (reference values: 0-0.4 µg/mL). Thus, in cases of slightly elevated d-dimer levels, one should not hesitate to start urgent PEX treatment in patients with clinically high suspicion of TTP if ADAMTS13 panel results are not obtained quickly. Thirdly, relapsed/refractory patients needed more PEX sessions to achieve first remission. A smaller number of PEX sessions to achieve response may be predictive of durable remission without relapse.
Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Alt... more Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion. Since CTNNB1 (β-catenin gene) exon 3 mutations were frequently detected in some rare fibrovascular lesions, we aimed to investigate the presence of oncogenic CTNNB1 mutations in SANT cases. For this purpose, 7 cases of SANT with typical histopathological features were retrieved. First, the presence of CTNNB1 exon 3 alterations was examined with a recently described immunohistochemistry-based method. Then, the findings were confirmed with polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), and Sanger sequencing. In all cases, immunochemistry of β-catenin gave a staining pattern that was suggestive of exon 3 alteration; however, no missense mutations were found in any case at the CTNNB1 exon 3 hotspot region. Subsequently, we screened for large interstitial deletions of CTNNB1 exon 3 which revealed short PCR products in three cases. Sequencing confirmed that these cases had large interstitial deletions, resulting in loss of the entire exon 3 of CTNNB1 . In the remaining four cases, loss of exon 3 was documented at the cDNA level, although genomic deletion was not identified. These results demonstrate that loss of CTNNB1 exon 3 and stabilization of β-catenin with activation of Wnt signaling pathway might have a significant role in the pathogenesis of SANT. Through this study, we provided important evidence for the neoplastic nature and pathogenesis of this disorder.
Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic li... more Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic lifelong disease, which could be manageable with tyrosine kinase inhibitor (TKI) drugs. The aim of TKI drug treatment is to provide age-and sex-matched duration of life in a given patient with CML. Personalized CML treatment with TKI drugs is the key strategy. Individual treatment approach includes the harmonization of CML disease characteristics, clinical experience, and best available clinical evidence. Specific CML disease characteristics in a given patient include; CML disease risk, comorbidities, molecular profile, compliance, lifestyle, and drug off-target risk profile. CML research evidence includes; randomized clinical trials indicating the data on the efficacy, safety, tolerability, toxicity, possible longterm adverse events, and pharmacoeconomy of TKIs. Clinical and physician experience includes TKI availability, TKI reimbursability, drug experience, adherence, and BCR-ABL1 monitorization facilities. The key decision of choosing a TKI of choosing TKIs for CML should be made via the consideration of these variables. The aim of this paper is to outline the latest 2016 World Health Organization definition of CML and its proper management with TKI-class drugs.
Introduction: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma with dist... more Introduction: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma with distinguishes clinical, biologic, and molecular characteristics. The MCL-International Prognostic Index (MIPI) incorporates age, EGOC performance status, normalized LDH level and WBC and has improved discriminatory power. The aim of this retrospective single-center study was to evaluate the clinical characteristics and response to treatment of patients with mantle cell lymphoma. Methods: This single center retrospective study included 297 adult patients diagnosed with MCL between December 2005 and May 2018. The diagnosis of MCL was rendered in accordance with the later World Health Organization (WHO) classification. Outcome was determined as response to treatment, progression free survival (PFS) and overall survival (OS) by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. We also compared the PFS and OS according to simplified MIPI (s-MI...
Retrospektif ozellikteki calismamiza 1996-2001 yillari arasinda bolumumuzde KML tanisi almis ve A... more Retrospektif ozellikteki calismamiza 1996-2001 yillari arasinda bolumumuzde KML tanisi almis ve Ankara Univeristesi Tip Fakultesi Hematoloji Bilim Dali Kemik iligi Transplantasyon Unitesinde kemik iligi nakli olmus 24 hastaya ait toplam 58 adet kemik iligi biyopsisi dahil edilmistir. Hastalara ait tani, nakil oncesi ve nakil sonrasi kemik iligi biyopsi, imprint ve kemik iligi aspirasyon materyalleri yeniden degerlendirilmistir. Calismada evreleme amaciyla orneklenen, tutulum bulundurmayan normoselluler 17 adet kemik iligi biyopsisi kontrol grubu olarak degerlendirmeye alinmistir. Kemik iligi biyopsi, imprint ve aspirasyon preparatlarinda KML fazi WHO-2001 kriterlerine gore belirlenmistir. H&E kesitlerde kemik iligi sellularitesi belirlenmistir. Biyopsilere retikulin derecelendirmesinin yapilabilmesi icin histokimya ile retikulin ve gerekli hastalarda trikrom boyalari, anjiogenezin degerlendirilebilmesi icin immunhistokimya ile anti-FVIII-RA boyalari uygulanmistir. Retikulin derecelendirmesi Bauermeister'in tanimladigi kantitatif kemik iligi retikulin degerlendirme semasi esliginde degerlendirilmistir. Anjiogenezin degerlendirmesinde ise, anti-FVIII-RA boyali preparatlarda morfometrik olarak, goruntu analiz sisteminde (Image Analysis System, Carl-Zeiss Vision GmbH, Hallbergmoas, Germany) KS-400 goruntuleme programi (Imaging System) ile damar alani, damar alaninin degerlendirmenin yapildigi alana orani ve damar sayisi olcumleri yapilmistir. Ayrica morfometrik olcumlerin yapildigi alanlarda alan sellularitesi ve megakaryosit sayisi belirlenmistir. Hasta ve kontrol biyopsilerinde hastalarin cinsiyeti, yasi, hastalarda tani, nakil oncesi, nakil sonrasi biyopsi ve kemik iligi nakil tarihleri belirlenmistir. Hastalarda kullanilan konvansiyonel tedavi protokolleri ve klinik bilgilerine ulasilmistir. KML hastalarinda yas, cinsiyet dagilimi literaturle uyumlu bulunmustur. KML gelisen hastalarda hastaliksiz kisilere gore kemik iligi genel ve alan sellularitesi, megakaryosit sayisi, damar alani ve damar alan oraninda ve retikulin derecelerinde artisin oldugu saptanmistir. Damar sayisinda ise nakil oncesi ve sonrasi degerlerde kontrol degerlerine gore yuksek sonuclar elde edilmistir. KML hastalarinda kullanilan konvansiyonel tedavi protokollerinin kemik iligi sellularitesi, damar sayisi, damar alani, damar alan orani, megakaryosit sayisi ve retikulin derecesine etkisinin olmadigi gorulmustur. Yanlizca nakil oncesi biyopsilerde hidroksiure-interferon- tedavisinin damar sayisinda artisi ile iliskili oldugu bulunmustur. Kemik iligi naklinden (KIT) sonra genel ve alan sellularitesi, retikulin derecesi ve megakaryosit sayisinin azaldigi saptanmis, bu parametrelerin KIT'den sonra kontrol grubuna yakin degerlere ulastigi tespit edilmistir. Bu sonuclar KIT'in KML hastaligini tam olarak tedavisini sagladiginin gostergesidir. Ancak vaskuler parametreler olan damar sayisi, damar alani ve damar alan oranlarinda KIT sonrasinda degisiklik gozlenmemistir. Bu sonucta KIT sonrasi erken donemde engrafman ve aktif proliferasyonun vaskuler parametrelerin yuksek bulunmasinda rol oynayabilecegini, bu nedenle kesin degerlendirme yapabilmek icin daha gec donem biyopsilerin de degerlendirilmesinin gerekliligini dusundurmektedir. Vaskuler parametreler olarak degerlendirmesi yapilan damar sayisi, damar alani ve damar alan orani degerlerinde tespit edilen artista retikulin dererecesi, megakaryosit sayisi, genel ve alan sellularitesi, hasta yasinin etkisinin olmadigi bulunmustur. Calismamizda farkli vaskuler parametreler anjiogenezin degerlendirmesinde kullanilmistir. Bu parametrelerin kendi aralarinda ve anjiogenezle iliskili oldugu bilinen diger parametrelerle yapilan karsilastirmalarinda tek basina damar sayisinin ele alinmasinin saglikli ve guvenilir bir yontem olmayabilecegi, anjiogenezin guvenilir olarak degerlendirilebilmesi icin morfometrik olarak damar alani, damar alan oran olcumlerinin damar sayimi ile birlikte kullaniminin daha anlamli olacagi sonucuna ulasilmistir. Anjiogenezin degerlendirilmesinde elde edilen bu sonuclar ile KML hastalarinda kemik iliginde anjiogenezin hastalikla birlikte belirgin artmis bulunmasinin konvansiyonel tedaviye yardimci olarak antianjiogenetik ilaclarin kullaniminin faydali olabilecegini dusundurmustur. Bunun kesin olarak gosterilebilmesi icin prospektif, genis hasta gruplarini iceren calismalara ihtiyac bulunmaktadir.
Aims: To determine the distribution of factor VIII related antigen, CD31, CD34 and CD36 in normal... more Aims: To determine the distribution of factor VIII related antigen, CD31, CD34 and CD36 in normal and malignant human vascular tissues using a panel of well characterised monoclonal antibodies.
Indian Journal of Hematology and Blood Transfusion, 2020
Purpose Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hemato... more Purpose Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hematological malignancy. There is still no standard treatment established for BPDCN patients. We aim to summarize the main clinical, biological features and treatment of 9 BPDCN patients. Methods Nine patients with BPDCN who had been diagnosed between July 2008 and December 2018 in Ankara University School of Medicine, were retrospectively evaluated. Results All patients (n = 9) were male, median age was 64 (21–80). Five patients (55.6%) had bone marrow infiltration, 5 patients (55.6%) cutaneous lesions, 6 patients (66.7%) lymph node involvement, 2 patients (22.2%) central nervous system involvement and 2 patients (22.2%) spleen involvement at time of diagnosis. Complex karyotype was observed in 2 patients. CHOP was given to 5 patients (55.6%), hyper-CVAD to 2 patients (22.2%), fludarabine, cyclophosphamide and mitoxantrone to 1 patient (11.1%) and cyclophosphamide, etoposide, methylprednisol...
Dear Editor, Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal ... more Dear Editor, Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal proliferation of histiocytes and skin manifestations are variable. Diffuse neonatal hemangiomatosis (DNH) has been described in patients with congenital self-healing reticulohistiocytosis (CSHR) and in very few cases of multisystemic LCH. Here, we present a rare case of LCH mimicking DNH and seborrheic dermatitis with multisystemic involvement. A 4-month-old female infant presented to our department with widespread erythematous and yellow scaly rash, accompanied by an intermittent fever for 2 months. These erythematous lesions first began on the inguinal region and disseminated all over the body. On physical examination, multiple discrete red-purple papules and white macules ranging in size from 0.3 to 0.8 cm, located mainly on the trunk and extremities, were identified. She had also orange-yellow scaly and crusted papules on the head and neck (Figure 1). Dermatoscopy revealed red struct...
Background: Recently Bergsagel et al have published a hierarchical model of myeloma evolution bas... more Background: Recently Bergsagel et al have published a hierarchical model of myeloma evolution based on cytogenetics and Cyclin (Cy) profiles. Previously we had reported flow cytometric expression profiles of these Cy and CDKI’s in unsorted marrow samples (Blood98 (11): 4230,2001) but had not been able to detect the parallelism between Cy-CDKI’s which we observed in the normals in the myeloma patients. Aim: Here in this study we aimed to analyze the same Cy and CDKI’s in marrow plasma cells by multiparameter immunocytochemistry and to evaluate the association with clinical parameters and impact on survival. Patients and methods: Fourty five myeloma patients diagnosed in our department between 1998–2004, aged 57(33–79), M/F:29/16 whose bone marrow biopsy specimens could be retrieved were included in the analysis. All patients were treated with VAD or MP as first line treatment. Staining was performed using monoclonal antibodies: Cyclins A, D1, p16, p21 (LabVision), Cy D3(DAKO) and Cy ...
Introduction: Several studies have attempted to describe the characteristics associated with larg... more Introduction: Several studies have attempted to describe the characteristics associated with large granular lymphocytosis (LGL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its clinical significance. However the clinical features of LGL lymphocytosis in the allo-HSCT setting is still sparse. The current study represents a detailed review of 667 patients transplanted in a single center with the objective to define the incidence of LGL lymphocytosis, to identify associations with transplant-related clinical parameters and to assess the impact on transplant related outcomes. Patients and Methods: During a 14-year follow up period (2005-2017) in this unicentric cohort study, we identified 19 patients (2.8%) with a significant LGL lymphocytosis, among 667 consecutive adult patients who underwent allo-HSCT. LGL lymphocytosis was defined as the presence of at least two of the following criteria: (1) sustained lymphocytosis above 3.0x109/L observed in at leas...
The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fou... more The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fourth edition of WHO classification of tumors of endocrine organs and the fourth edition of WHO classification of tumors of hematopoietic and lymphoid tissues are recently published. The updates in both fields include some new disease descriptions and prognostic markers. Our aim in this review article is to give practical diagnostic information about the most frequently seen hematolymphoid involvements of the pituitary gland, thyroid, and adrenal tissue. We designed the text in the order of organs and the contents according to the disease frequency. The pituitary gland and cellar region are the most frequently involved with Langerhans cell histiocytosis. Although it is very rare, Erdheim-Chester disease has recently been included in the classification and still needs more clear diagnostic definitions. Lymphoproliferative thyroid lesions and presentations create diagnostic problems for the ...
Virchows Archiv : an international journal of pathology, Jan 9, 2017
Our aim in this study was to describe the clinical, morphological, and molecular profile of gastr... more Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years...
Çok az sayıda izole kemik tutulumu ile ortaya çıkan saçlı hücreli lösemi olgusu bildirilmiştir. B... more Çok az sayıda izole kemik tutulumu ile ortaya çıkan saçlı hücreli lösemi olgusu bildirilmiştir. Biz burada izole kemik lezyonları olan bir saçlı hücreli lösemi olgusunu bildiriyoruz. Hastanemize 48 yaşında bir erkek 3 yıldır olan sol diz ağrısı ile başvurdu. Hastanın önceki şikayetleri sırasında manyetik rezonans görüntüleme yapılmış olup herhangi bir patolojik bulguya rastlanmamıştı. Direkt röntgen incelemede tibiada kistik infiltratif bir lezyon gözlendi. Hastanın bilgisayarlı tomografi görüntülemesi ılımlı splenomegali dışında normaldi. Tüm vücut pozitron emisyon tomografisinde kemiklerde çok sayıda patolojik tutulum mevcuttu. Kemik iliği biyopsisi ve aspirasyonun morfolojisi ile akım sitometrisi herhangi bir tutulum olmaksızın normaldi. Bunun üzerine tibiadaki lezyondan kemik biyopsisi yapıldı. Yapılan kemik biyopsisinin morfolojisi tipik saçlı hücreli lösemi ile uyumluydu. İmmünhistokimya sonuçlarında güçlü CD20, CD25, anneksin A1; soluk siklin D1 pozitifliği ve %5'ten daha az Ki 67 proliferasyon indeksi saptandı. Sanger sekans yöntemiyle yapılan moleküler analizde saçlı hücreli lösemi tanısını destekleyen BRAF V600E mutasyonu gözlendi. Hasta 7 gün 0.1 mg/kg kladribin ve ek lokal radyoterapi aldı. Hasta 3 yıl sonra hala remisyonda olup ilerleyici lezyonları bulunmamaktadır. Sonuç olarak, saçlı hücreli lösemi hastalarında nadir bir ortaya çıkış şekli olan izole kemik tutulumuna tanısal araç olarak BRAF V600E mutasyonuna dikkat çekmek istiyoruz.
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (D... more As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil,
Addressing the global burden of cancer, understanding its diverse biology, and promoting appropri... more Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the World Health Organisation, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UNdefined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterised by a validated prognostic gene expression score (p<0.0001), but International Prognostic Index-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.
Bu calismada patoloji arsiv materyalinden elde edilen DNA ornekleri ile yeni nesil dizileme tekno... more Bu calismada patoloji arsiv materyalinden elde edilen DNA ornekleri ile yeni nesil dizileme teknolojileri kullanilarak JAK2 ekzon 12 ve ekzon 14 (JAK2V617F) ve MPL ekzon 10 (MPLW515L, MPLW515K, MPLA506T ve MPLA519T) mutasyonlarinin arastirilmasi ve patoloji arsiv materyallerinde mutasyonlu hucre orani hastalik prezentasyonu iliskisinin tespitinde yeni nesil dizileme teknolojilerinin duyarliligi arastirilmistir.Ankara Universitesi Tip Fakultesi Patoloji Anabilim Dali’da 2001-2011 yillari arasinda kemik iligi biyopsi ve yayma preparatlari incelenen BCR ABL negatif MPN (ET, PV, PMF) tanisi almis hastalar calismaya alinmistir. JAK2 ve MPL mutasyonlarini saptamak amaciyla yeni nesil dizileme (pirosekanslama) yontemi kullanilarak molekuler analiz gerceklestirilmistir.Yas, cinsiyet dagilimlari ile laboratuvar bulgulari hastaliklarin evreleriyle beklenen sinirlar iceriside bulunan serimizde tum olgularin % 66.6’inde JAK2 ekzon 14 V617F mutasyonu bulundugu ve % 33.4 olgunun yabanil tip oldugu saptanmistir. JAK2 ekzon 12 mutasyonu ve MPL ekzon 10 mutasyonu ise sadece iki ayri ET tanili olguda (% 1.75) saptanmistir. ET (% 69.6) ve PMF (% 55.6) tani gruplarinda JAK2V617F mutasyonu klasik kaynaklarda bildirildiginden daha yuksek oranda, PV (% 75) olgularinda ise daha dusuk oranda bulunmustur. JAK2V617F-pozitif klonunun buyuklugu anlaminda olan “Allel burden” orani en dusuk PMF olgularinda, bunu izleyen oranda ET ve en yuksek PV olgularinda bulunmustur. Sellularite ve kan lokosit duzeyleri ile allel burden orani arasinda anlamli iliski saptanmistir. Bu calismada kemik iligindeki tum farkli klonlari iceren materyallerde, yeni nesil dizileme teknolojisinin metot olarak tercih edilmesindeki en onemli avantajlarindan biri olan allel burden durumunuun yuksek hassasiyet ile tespit edilebildigi gorulmustur.AbstractIn this study, we aimed to investigate JAK2 exon 12 and JAK2 exon 14 (JAK2V617F) mutations and MPLW515L, MPLW515K, MPLA506T and MPLA519T mutations, on DNA extracted from pathology archieve materials using Next Generation Sequencing Technologies. Also we aimed to evaluate the relationship between disease presentation and the“allele burden” ratios by this molecular analysis on bone marrow samples.The bone marrow biopsies and smears diagnosed as BCR ABL negative MPN (ET, PV, PMF) between 2001-2011 in Ankara University Faculty of Medicine Department of Pathology were selected for the study. The molecular analysis by using Next Generation Sequencing (pyrosequencing) was performed for detection of JAK2 and MPL mutations.Our series showed compatible age, gender and laboratory findings with the stages of the diasease groups. JAK2 exon 14 V617F mutation was examined in %66.6 of the patients. JAK2 exon 12 mutation and MPL exon 10 mutation was examined only on two distinct ET case (%1.75). The diagnostic groups ET (%69.6) and PMF (%55.6) in our series were presenting higher JAK2V617F mutation compared to the classical literature. In the PV (%75) group the mutation ratio was lower than the classical literature. “Allel burden” which represents the amound of JAK2V617F mutated clone ratio was lowest among PMF cases, followed by ET. The ratio was highest among PV cases. A positive relation between cellularity, blood leokocyte levels and allel burden was examined. We determined that performing the next generation sequencing method for the bone marrow samples which contain all of the different clones, has the advantage of giving information on detection of allel burden status with high sensitivity.
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