Amity Institute of Biotechnology: Topic-Leukemia (2017-2018)
Amity Institute of Biotechnology: Topic-Leukemia (2017-2018)
Amity Institute of Biotechnology: Topic-Leukemia (2017-2018)
BIOTECHNOLOGY
NTCC REPORT
TOPIC-LEUKEMIA
(2017-2018)
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TABLE OF CONTENT
1. ABSTRACT
2. INTRODUCTION
3. TYPES OF LEUKEMIA
4. GENETICS
5. RISK FACTORS
6. SYMPTOMS
7. DIAGNOSIS
8. TREATMENT AND THERAPIES
9. CLINICAL TRIALS
10. REFERENCES
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ABSTRACT-
Leukemia one of the most deadly disease was first described in 1827 by DR. Alfred-
Armand-Louis-Marie-Velpeau. It was further described by pathologist Rudolph Virchow in
1845.
Many significant researches and clinical trials in the field of its cause, prevalence, treatment
and prognosis have been going on since ever.
Due to change in lifestyle, this has become one of the fastest growing disease in the world.
Around $5.4 billion (USD) is spent in United States on the treatment of this disease every
year. Though leukemia can be treated, it still has highest number of death rates in
comparison with other types of cancer. The side effects of the treatments and therapies are
so adverse that in most cases patient faces depression and mental breakdown. A complete
recovery from the disease and the side effects takes almost half a decade in some cases as
patient, though cancer free still have to go for regular check-ups.
This report gives you a brief introduction of leukemia along with its subtypes, risk factors,
symptoms, therapies and clinical trials.
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INTRODUCTION
Blood cancer or Leukemia (lk.) is the cancer in body’s blood synthesizing system, which includes
bone marrow and lymphatic system. There are several categories of blood cell, which are blood cells
(WBC), Red blood cells (RBC), and Platelets. Leukemia involves cancer of the WBC’s. White Blood
cells are of two type:
White Blood cells are the weightiest part of our immune system. These cells are made in the bone
marrow but some types of WBC’s are also synthesized in thymus gland, spleen and lymph nodes.
WBC’s are the most formidable and dominant infection and contagion fighters of our body. When, a person
has leukemia, the bone marrow is not able to manufacture normal white blood cells which disrupts their
proper functioning.
This disease damages the DNA (Deoxyribose nucleic acid) of the new immature white blood cells. Due to
this, it causes continuous division and growth of abnormal cells, which increases their count tremendously.
These abnormal cells replaces the proper healthy blood cells making it tough for the blood to function
normally.
After a certain period these healthy blood cells starts dying and replaces themselves with new abnormal
blood cells which are being produced in bone marrow. These abnormal cells do not degenerate and die;
rather they keep on accumulating and occupying space. As, these cancer cells keep on growing over a
period it eventually stops the production of healthy white blood cells . Thus, the bad abnormal cells crowd
over the good normal cells. This leads to one of the deadliest disease called Leukemia.
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TYPES OF LEUKEMIA
Leukemia (Lk) is divided in four main categories –
Chronic Lymphocytic (or Lymphoblastic) Lk.
Acute Lymphocytic (OR Lymphoblastic) Lk.
Chronic Myeloid (OR Myelogenous) Lk.
Acute Myeloid (OR Myelogenous) Lk.
Leukemia is segregated on the basis of type of WBC’s which are – Lymphocytes OR myeloid cells and
with the pace with which disease is getting developed i.e. - very quickly or acute disease OR slowly over
time or chronic disease.
Lymphocytic leukemia – This type of Lk. gets developed from cells which produces natural
killer (NK) cells, T lymphocytes (T cells), B lymphocytes (B cells). Each cell is unique and perform a
special function for our immune system. Some of them produces antibodies while others readily fights and
directs other immune cells to fight infections.
Myeloid leukemia –This type of Lk. gets developed from cells which produces WBC’s also called
monocytes and granulocytes. Granulocytes are named after the enzyme which are packed in granules that
they carry inside of them. These enzymes are released when the cells encounter with invading fungi and
bacteria. Monocytes then convert into macrophages, which destroys and engulf the invading organisms.
B cells and T cells plays a vital role in immunising the body against the germs, viruses and
infections, further it also destroys the cells that have been infected. B cells in particular prevent
the germs from infecting the body while T cells fight and destroy the infected cells.
Although, there is no particular age for the occurrence of acute lymphocytic leukemia, but it is
most common for people below 15 years of age or above the age of 45.Children takes up largest
portion of percentage in ALL diagnosis specifically the ages between two to four, it is very rare
among the adult to develop this category of cancer.
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2. ACUTE MYELOID LEUKEMIA (AML) –
This is the most common type of acute leukemia. It occurs when the bone marrow start making
blasts, cells that have not completely matured. These blasts normally develop into white blood
cells. However, in AML, these cells do not develop and are unable to obviate infections.
When a person has AML, the bone marrow sometimes also starts making platelets and abnormal
red blood cells which further complicates the disease. The number of these abnormal cells
increases rapidly and so these cells begin to crowd out the normal white blood cells, red blood
cells and platelets that the body needs.
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How does leukemia
Develop? Is leukaemia
hereditary?
The exact reason or cause of leukemia is still unknown but some researches and studies have shown that it
has been evolved from combination of factor. These factors mostly include environment, genetic, chemical
exposure and lifestyle. Generally, a person with leukemia acquires a change or mutation in the DNA of
cells which causes their abnormal growth and lose of typical functions of white blood cells.
It is not clear what causes the mutations to occur. Chromosome translocation is the term used when
there is change in cell’s DNA that is quiet common in leukemia. It is a condition in which, a part of
chromosome breaks and gets itself attached to another chromosome. For example, one of the most common
type of translocation which is seen in all cases of CML and a few times in other types of leukemia is the
interchange in DNA of 9th and 12th chromosome, this leads to formation of Philadelphia
chromosome. Thus creating an oncogene or a cancer-promoting gene also called BCR-ABL. This
change in the DNA of the chromosome cannot be inherited by progeny but occurs only in the life of
individual affected by leukemia.
Mostly, leukemia cases are not believed to be called hereditary but sometimes and under certain conditions
genetic mutation passes down from parents to offspring. Thus increasing the chances of developing
Leukemia.
Li-Fraumeni is a condition which is characterized when offspring inherits mutation in the tumour
suppressor gene. This gene is gene is also called TP53. In this condition, an individual develops, a high risk
factor of developing leukemia or some other types of cancer. Noonan syndrome, Down syndrome,
Neurofibromatosis type 1 and Ataxia telangiectasia are some of the other prominent hereditary condition
that increases the risk factor of developing leukemia.
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Leukemia risk factors
1. GENERAL
Age: Age is a major risk factor that plays role in leukemia; increase in the age increases the
chances of developing the disease. However ALL category is an exception to this rule.
Gender: AML, CML and CLL are more prone in men than women are more likely to develop
CML, CLL and AML than women.
2. GENETICS
Family Related: Leukemia rarely have familial link, however, people who have first degree relation
with CLL patients might be at risk. Similarly if a sibling or one of a twin who had AML or ALL
may put the other sibling at high risk of developing the disease.
Genetic diseases: Down syndrome, Klinfilters syndrome, Noonan syndrome and other such genetic
abnormalities also increases the risk of leukemia.
3. LIFESTYLE
Smoking may not directly cause leukemia but it contains the chemicals that increases the risk of
developing the disease.
4. EXPOSURES
Radiations: Exposure to energy radiations both high and low from atomic bombs, electromagnetic
fields etc. may also risk of developing the illness.
Chemicals: Long-term Exposure to industrial bleach, toxicants pesticides and chemicals also add
up to the risk.
5. PREVIOUS TREATMENT
Sometimes therapies and treatments like radiation, chemo, etc. are also considered as a risk factor.
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Leukemia symptoms
Some general symptoms of leukemia include:
Frequent infections
Abdominal discomfort
Headache
Fever chills
Fatigue
weakness
Loss of appetite
Night sweats
joint pain
Shortness of breath
Easy bruising
Easy bleeding
small red spots under the skin
Weight loss
Thrombocytopenia: It is a term used when there is low platelets count in blood. The
main function of Platelets is that it helps in blood clotting thus preventing easy bruising and
bleeding.
Anemia: It is a term used when the RBC’s count is low in blood. The function of red blood
cells is to carry oxygen in the body therefore this condition may lead to weakness, shortness of
breath and fatigue.
Swollen lymph nodes: Leukemia also show signs like swelling of armpits, groin and
neck. This stage arrives when leukemia has reached the lymph nodes.
Leukopenia: It is a term used when the WBC’s count is low in blood. Due to low count of
these cells the immune system weaken thus making the body prone to infection.
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Diagnosis of leukemia
The process of diagnosing Leukemia begins with visiting a doctor for a routine test when there is
problem in blood sample. He/she may ask the patient about symptom and take a physical exam.
Sometimes doctors also ask about your health history .On the basis of this information he may
recommend you to a specialist or some other tests for leukemia.
Health history
Records of one’s symptoms, medical events, risk factors and other medical condition and problems are
known as person’s health history. While taking a person’s health history following questions might be
asked-
Blood Disorder
Viral Infection
Previous radiation or chemo therapy
Genetic syndrome – Down syndrome, Bloom syndrome, Fanconi anemia etc.
Exposure to radiation and chemicals
Family genetics
Physical exam
Checking of vital signs- shortness of breath, fever, rapid heartbeat
Feeling area around neck, groin, armpits for swelling and enlargement of lymph nodes
Feeling abdomen for swelling of organs
Mouth and gum examination for bleeding infection and swelling
Examination of skin for paleness and bruising
Diagnosing of leukemia takes long, so it’s normal to worry but it’s also important to make sure that
other health conditions are ruled out because there are many similar symptoms.
Sometimes symptoms turn so severe and rapid that diagnosis proceeds rapidly, and the patient have to
be immediately admitted in the hospital to instantly start the treatment.
The following series of tests are recommended by the doctors for detection of leukemia and its stage
or in other words how far has it progressed.
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COMPLETE BLOOD COUNT TEST
This test measures the quality and number of RBC’S, WBC’s, and platelets in blood. In conditions like
leukemia the blood cell count is abnormal. Blasts are immature blood cells which are not normally
seen in blood, so a doctor might suspect leukemia if there are blast or cells do not look normal.
If the level of the following chemicals are high in blood it may indicates leukemia-
Creatinine
Blood urea nitrogen
Phosphate
Alanine Aminotransferase(ALT)
Uric acid
Aspartate aminotransferase (AST)
fibrinogen level
prothrombin time
CYTOCHEMISTRY
Cytochemistry helps the doctor to identify the type of cells that are present in the blood. It is done by
using stains or dyes which help in determining the blood components and structure of tissues in blood.
In this test only certain types of stains are used as they are attracted to the chemicals found in leukemia
cells.
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IMMUNOPHENOTYPING
Leukemia subtypes can be detected by using immunophenotyping. This technology is used to study
the protein of cells, by a specific antigen-antibody reaction which identifies it. Specific enzymes and
fluorescent labels are used to mark monoclonal antibodies which binds only to specific antigens.
Leukemia cells or Blasts can be seen through enzyme or fluorescent label. Thus, detecting the type of
Leukemia.
FLOW CYTOMETRY
Cells can be sorted and classified by using fluorescent labels on their surface, this technique is called
flow cytometry. In this test, laser light is made to pass through the cells, which is then analyzed and
measured by computer. This helps the doctor to collect and compile the data of many cells rapidly from
the same sample as well as it also helps to view the antibodies.
Leukemia cells or Blasts have unique features which helps the doctor in forming a prognosis report
and measuring the effectiveness of treatment using Minimal Residual Disease (MRD). The presence
of MRD signifies that there are blasts in bone marrow that cannot be seen through standard lab test
technology but can only be seen by using more sensitive tests like Polymerase Chain Reaction (PCR)
or flow cytometry test.
Microscope can help in finding the abnormalities in chromosome but changes in DNA can be studied
by more powerful microscope and closer analysis of molecules which includes technologies such as
polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH).
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Polymerase chain reaction (PCR) –
It is a technique through which multiple copies of a particular gene is made so that it can be used for
testing in lab. PCR helps in finding out the mutation, deletion and inversion in DNA and whether they
are linked with certain type of leukemia. It is also helpful in determining the type and prognosis of
leukemia.
LUMBAR PUNCTURE
This procedure is performed to check whether the cancer has spread to spinal fluid. In Lumbar
Puncture, a small amount of cerebrospinal fluid is extracted from the space around spine and is
observed under microscope. CSF fluid is found around the spinal cord and brain.
CHEST X-RAY
Small doses of radiations are used to make an X-Ray image on film of body’s structures. It is used to
find -
enlargement of lymph nodes in centre of chest also known as mediastinal lymph node
presence of fluid between lung and wall of chest called pleural effusion
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CT SCAN
A CT scan also known as Computed tomography uses technology of X-Rays to make 3D images of
tissue, organs, blood vessels and bones inside the body. Doctor uses CT scan to check the condition of
liver and spleen and if they are in normal size or not, It is also used to scan the lymph nodes near
trachea, around the heart and in the abdomen are enlarged or not. The enlargement of lymph nodes
points that a person might have leukemia.
MRI
Magnetic resonance imaging (MRI) works on technology of radiofrequency waves and magnetic forces
to make sectional images of tissue, bones, organs and blood vessels. Doctor uses MRI scan when they
think that leukemia has spread in brain. Computer helps to turn the images into 3D pictures.
ULTRASOUND
Internal Organs such as liver, spleen and kidney can be checked if they have been affected by leukemia
using ultrasound. In this high frequency sound waves are used to make images of different body organs.
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TREATMENT AND
THERAPIES
Treatment for leukemia involves a special healthcare care team who make different treatment plan for
different patients depending upon their needs and condition. Sometimes, a combination of different
treatments is given to the patient, while deciding the treatment the following things are considered-
patients age
type of leukemia
chromosomal abnormalities or any other genetic disease
overall health condition
In human body, cells are constantly replaced by dividing and growing however when cancer occurs
this growth and division becomes uncontrolled. As more and more cells are produced, they start
occupying a lot of space which was previously inhabited by healthy and useful cells.
In chemotherapy a single drug or combinations of drugs are used which inhibits the cancer cells ability
to grow and divide. These drugs can be given in two ways i.e. directly into the blood so that cancer
cells are attacked throughout the body, or they are targeted at cancer specific site.
They target the food source of cancer cells that is the hormones and enzymes.
Inhibits mitosis or cell division.
Triggers apoptosis i.e. suicide of cancer cell.
In order to starve the tumour growth of new blood vessels are stopped.
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HOW LONG DOES IT LAST-
Patients will need chemotherapy regularly over a period of time for best results, or as it has been
suggested by the oncologist.
The healthcare team along with your doctor draws a specific plan of the treatment sessions and for how
long will it occur. The course of treatment can start from a single dose per day to a few weeks. This
however depends on the stage and type of leukemia.
If a patient needs more than one course of treatment, the body needs to be rested so that it is recovered
for the next dose. For example, a treatment session can occur on one day, followed by one week rest,
and then another session on a day followed by three week rest period. This cycle may be repeated many
times over.
A psychologist must be available to help the patient in dealing with physical mental and emotion
ordeals and side-effects of the therapy.
The drugs and chemicals used in chemotherapy are broken down or metabolized in the liver. Thus,
overwhelming the liver which leads to range of secondary effects.
It is necessary to do blood test before the treatment so that if the cell count of platelet, WBC’s, RBC’s
are low the treatments need to be delayed. Regular blood test also ensures that other organs are
functioning properly and if there is any prognosis in the treatment.
WAYS OF CHEMOTHERAPY
o Orally- If a patient is in early stages and healthy enough, oral tablets can be taken at home.
However it is still compulsory for patient to make regular visit to hospital for regular check-up
of health and response to the treatment. The drugs can be in the form of liquid as well as a
capsule. One must be very particular of time while taking the drug however if patients forget to
take the dose at specific time, one should immediately contact the healthcare team.
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The drug can also be given-
Intrathecal- in this the drug is injected in between the layers of tissue which covers the spinal
cord and brain.
Intraperitoneal- in this drugs are directly injected in part where intestine, liver and stomach are
located.
Intra-Arterially- the drug is directly injected into artery which leads to cancer cells.
The drug is injected through a needle or drip or pushed through a pump, to ensure a uniform rate of
delivery. A catheter, portacath and a central line are devices used to deliver the drug solution.
There are various types of drugs available for chemotherapy. These drugs are divided into four major
categories-
Alkylating agents- Drugs in this category directly attacks the cell DNA and can kill it at
any stage of its life cycle. For Example- busulfan, cyclophosphamide, thiotepa, chlorambucil etc.
Antimetabolites- These drugs copies the protein which are needed by the cell however
when the cell consume this protein they do not offer more and the cells starts starving. For
example- pyrimidine antagonist, folate antagonists, purine antagonist.
Plant alkaloids-These drugs destroys the cells ability to divide and grow. For Example-
doxorubicin, actinomycin, mitomycin.
Antitumor antibiotics- These drugs bind themselves with DNA and stop the synthesis of
RNA thus stopping the production of cell. For Example- mitoxantrone, bleomycin, doxorubicin.
SIDE EFFECTS
Chemotherapy have severe adverse effects as it not only targets the cancer cells but also the healthy
cells of the body. The patient must know what to expect before starting the treatment-
FATIGUE
Fatigue is one of the most common side effect, which is present most of the time and sometimes after
certain activity. Patient are generally advised bed rest and to avoid task that can cause stain or are
overtiring.
Severe tiredness must be immediately reported to doctor as it signifies anemia i.e. low RBC count.
HEARING IMPAIREMENT
Chemotherapy uses drugs that have toxic effect, so it can lead to temporary or permanent hearing loss
in some.
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LOW RBC COUNT OR ANEMIA
RBC’s act as oxygen carrier to all tissues in our body. Low RBC count leads to heart palpitation,
tiredness, breathlessness. Patients with acute anemia may require blood transfusion.
Blood cell count can increase by taking food rich in iron like green leafy vegetables, meat, raisin and
apricot. Erythropoietin is a drug that also helps in increasing the red blood cell count.
LOSS OF APPETITE
Chemotherapy generally weakens the body’s metabolism, leading to reduce in appetite along with
instant and excessive weight. This may last till the treatment is finished and cancer remises.
One may take smaller and frequent meals to keep themselves nourished. Liquid intake of juices and
other fluids may help.
They can also turn into more bone marrow cells. In leukemia and other blood disorder our body is
unable to develop healthy and normal hematopoietic cells. Now if the body is unable to produce normal
and healthy stem cells, the blood cells that are produced from these hematopoietic cells are also
improper and unhealthy. This causes disease like leukemia and other genetic abnormalities.
In a stem cell transplant, new and healthy stem cells are planted in our body which helps in making
healthy and normal blood cells.
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TYPE OF STEM CELL TRANSPLANT
But before this healthy stem cells are extracted from the body and kept in frozen state. After
going through the chemo and radiation therapy, frozen stem cells are thawed and put back in
blood through an IV tube.
It usually take complete 24 hours for the stem cells in reaching the bone marrow and beginning of its
function i.e. they start multiplying and grow healthy blood cells.
Allogeneic transplantation-
Also known as an ALLO Transplant. In this stem cells of another healthy individual are
extracted and planted into the patient. However in such cases it becomes necessary to find out
a matching bone marrow because of the presence of protein called human leukocyte antigen
(HLA) in WBC’s.
The HLA protein must match otherwise there can be complications and disease like the graft-
versus-host disease (GHVD). In this disease, healthy cells extracted from transplant starts
attacking the body. Best matches are found among the family member especially your sibling.
Once a matching donor is found, you can undergo a chemo and radiation therapy. After this
healthy stem cells of another person can be transplanted through IV tube.
3. RADIATION THERAPY
In this therapy, powerful waves of energy like X-rays or other high energy beam are used to
damage as well as disrupt the growth and division of leukemia cells. It also slows its growth
rate and shrink tumours so as to enable a surgery.
Radiation Therapy can go on as a single treatment method as well as with combination in with
chemotherapy depending upon the stage and type of cancer. Almost 65% of people suffering
from leukemia undergoes a combination of both the therapies so as to enhance the treatment.
Ionizing radiation is a high energy type of radiation which is used in the therapy. Research and
studies on to understand the working of radiation is still going on but on a simpler level radiation
breaks the complex cell DNA of cancer cells and inhibit their growth and division sometime
even killing them.
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SIDE EFFECTS
Radiation therapy not only effects the cancer cells but also non-cancerous cells. Thus side effects of
radiation therapy are often found similar with chemotherapy. Side effects of radiation therapy can be
divides as two-
Hair loss
Loss of appetite
Depression
Stiffening /restricted movement of neck jaw and other body parts. Sometimes doctor also
advise physiotherapy as tissue and muscles are damaged during radiation therapy.
Skin problems- red and purple spidery appearance of skin due to dilated capillary, itching
and slow healing of wound.
Diarrhoea- radiation therapy can damage the bowel moment and sometimes
accompanied by blood.
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CLINICAL TRIALS
Clinical trials are the research and studies going on in finding new treatments and therapies to
treat cancer. It helps in providing information about the effectiveness and safety of new ways of
treatment of the disease and whether they should be made available and legal. No treatments can be
executed if they are not shown to be safe and effective. This can only be shown by clinical trials.
Any person who is suffering from the disease or is at risk of developing the disease can take part in
clinical trial.
The research team is made up of scientists, research assistants, nurses, health care professionals
and doctors. A special team of clinical research is also available who monitors the health of patient
and help them understand what will during the trial procedure.
The importance of clinical trial is that it helps in making the progress in the field of the disease,
which may be more effective and curable. Many people have successfully gone through the trials
and are living long, healthier and happy. Finding and studies from the trials have been progressive and
led to –
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REFERENCES
1. https://www.lls.org/disease-information/myeloma/treatment/f
2. https://www.lls.org/disease-
information/myeloma/treatment/follow-up-care
3. https://www.medicalnewstoday.com/articles/142595.php
4. https://www.mayoclinic.org/diseases-
conditions/leukemia/symptoms.../syc-20374373
5. https://www.medicinenet.com/leukemia/article.htm
6. https://medlineplus.gov › Health Topics
7. https://www.nature.com/leu
8. https://www.journals.elsevier.com/leukemia-research/recent-
articles
9. https://www.omicsonline.org/leukemia.php
10. https://www.sciencedirect.com/journal/leukemiresearch
11. https://www.cancer.gov/types/leukemia
12. https://www.allbloodcancers.org/current-news
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