Dr. M. B. Agarwal
What is Leukaemia?
Leukaemia is blood cancer. Our bone marrow produces blood and blood cancer begins from the bone marrow. There are three types of blood cells and Leukaemia is cancer of the white blood cells.

What is Chronic Myeloid Leukaemia and how common is it?
There are four main types of leukaemia. Two of them are acute and two are chronic. The Acute Leukaemias are Acute Myeloblastic Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL) while the Chronic Leukaemias are Chronic Myeloid Leukaemia (CML) and Chronic Lymphocytic Leukaemia (CLL). Acute leukaemia develops quickly while Chronic Leukaemia develops slowly. In CML, white cells are present in excess. Their production goes out of control. These cells fill the bone marrow and also come out in the blood.
CML is the commonest blood cancer in India and other Eastern countries. CLL is the commonest blood cancer in Western countries.

What is the age at which CML occurs?
In India, most commonly, CML affects the age group between 30-60 years. In the Western world, it affects the age group between 50-70 years. Rarely” it can occur in children and very old persons as well. It affects both males and females.

Is CML a genetic disease? If I have it, will my children have higher chance of getting it?
No. CML is not a genetic disease. Children or any other member of the household has no higher chance of getting it. CML is not inherited.

Is CML a contagious disease? Can It spread to my spouse, parents or children?
No. CML is not an infection and hence it is not a contagious disease. It cannot spread to other members in the house.

Why did I get CML? What are the risk factors?
The exact answer to your question is unknown. In Japan, after the atom bomb explosion at Hiroshima and Nagasaki, a large number of affected individuals developed CML after a few years. Hence, there is a role of radiation. A nuclear accident can result into CML. However, in routine civil life, the reason one gets CML still remains under research. During the course of day to day living there is no way one would be exposed to the kind of radiation that would result in CML.

Also, exposure to certain chemicals, especially benzene over a period of time can result in blood cancers including CML. Benzene is a chemical in petrol and used in the rubber industry. However, exposure to petrol etc. in routine civil life cannot produce CML.

What is the Philadelphia chromosome?
We have 23 pairs of chromosomes (genetic material). In CML, the genetic material from chromosome 9 and 22 get translocated resulting into a shortened chromosome 22. This produces a new gene called bcr-abl. This shortened chromosome 22 was first detected in 1960 by scientists in the city of Philadelphia. Since then, the so called Philadelphia chromosome has been shown to be a consistent finding in patients of CML. This is of diagnostic importance.

Was I born with Philadelphia chromosome?
No. One is not born with the Philadelphia chromosome or bcr-abl gene. It develops later on. Bcr-abl leads to excessive production of an enzyme (protein) called Tyrosine Kinase (TK) which causes increase in white cells.

What are the symptoms of CML?
CML may not have any symptoms as it develops slowly. Many patients are diagnosed during routine blood tests carried out for one reason or the other.
Symptoms of CML are vague. Tiredness, weight loss, excessive sweating, fullness in the left upper part of the stomach, discomfort or lump in the same region and feverish feeling may occur. These symptoms are very common while CML is rare.

Once the disease is advanced (for example after few years into blastic phase), there can be anaemia (lack of blood) leading to pale appearance, bruises on the surface of the skin due to
bleeding, infection leading to fever and development of glands in the neck or at other areas (lymphadenopathy).
How is CML diagnosed?
Usually, CML is suspected because of enlarged spleen (lump in the left upper part of stomach). The GP or your family physician, in such cases would ask for blood counts which in turn may show an increase in white cell counts. Please remember that the increase in white cells most commonly occur also due to infections causing fever, cough and diarrhoea etc. Hence, one should not get unduly worried just because the white cells are more.

Subsequently, the haematologist or medical oncologist will look at the type of blood cells and also carryout bone marrow examination looking for the presence of Philadelphia chromosome or bcr-abl gene which will confirm the diagnosis.

Cancer has stages. Does CM L also have stages?
Chronic Myeloid Leukaemia has phases i.e. chronic phase, accelerated phase and blast phase. These phases maybe loosely called stage 1,11 and III or early, intermediate and late.

Most of the patients are diagnosed in the Chronic phase or early phase itself. The disease remains stable for years during which there are not many complaints and one can work normally. It is during this phase that the treatment is started which is usually in the form of oral pills (Glivec-lmatinib) taken daily. No one requires hospitalization in the Chronic phase. During this phase, there are very few or no blast cells in the blood or marrow.

The next phase is the Accelerated phase which can sometimes develop very rapidly. In this phase, there are more blasts in the blood or marrow. The patient feels more weak and tired. He may also develop fever (infection) or bleeding. Spleen becomes larger and may stop responding to treatment.

Subsequently, the Blast phase develops. This is like acute leukaemia. Here, the number of blasts in the blood or marrow is maximum. Patient becomes very weak and often requires blood transfusion and even hospitalization.

How is CML treated?
Chronic Myeloid Leukemia is a form of blood cancer arising from a specific cell, referred to as a stem cell, which give rise to series of different cells including the myeloid cells both in normal and abnormal states. Hence it is sometimes referred to as a stem cell disorder. The reason for initiation and progression to a cancerous process is because of the acquisition and persistence of a specific abnormality within the stem cells.

This abnormality is related to the chromosomes, which are again specific to the 9th and 22nd chromosomes. Because of rearrangement in some chromosomal materials within these two sets of chromosome an abnormality develops resulting in the form of generation of an abnormal protein called the BCR-ABL fusion protein which has unregulated enzymatic activity and eventually causes the proliferation of the cells, driving the progression of the disease.

It is this proliferation that manifests as high counts with spleen enlargement and constitutional symptoms typical of CML.

The objective of treating CML therefore revolves around blocking the activity of this protein using small molecules thereby gaining control of the disease by suppressing the protein activity and allowing the existing normal stem cells to function.

However, this suppression can only occur after sustained and prolonged therapy with these small molecules, which are referred to as tyrosine kinase inhibitors of which we are more familiar with Imatinib, Nilotiniband Dasatinib.
    
Compiled for: Max Friends
Source: Max Foundation