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Chronic Myeloid Leukemia (CML)  


Chronic myeloid leukemia(CML)is a cancer of the blood and bone marrow, occurring primarily in adults aged over 50 years with a slight male predominance. Although its causes are not well known, the disease is favored by exposure to benzene and ionizing radiation.CML represents 15-20 % of adult leukemia.Being associated with a genetic abnormality, chronic myeloid leukemia is characterized by excessive production of white blood cells or overgrowth of myeloid cells in the bone marrow. In order words, the cancer begins by causing abnormal growth in the blood-forming tissue of the bone marrow.  


Chronic myeloid leukemia is one of four major myeloproliferative disorders:
Polycythemia vera – too many
 red blood cells in the bone narrow
Chronic Myeloid Leukemia – see above
Essential thrombocythemia -
 increased number of platelets  

Primary myelofibrosis or myeloid splenomegaly – malignant tumor of blood-forming tissues in the body 


Symptoms of Chronic Myeloid Leukemia 


The onset of chronic myeloid leukemia is insidious and some cases are discovered incidentally during a routine blood count in apparently healthy subjects. 

 

1) General Symptoms - The condition tends to be asymptomatic at the beginning. Fever is absent or reduced; yet the patient experiences fatigue, sweating, loss of appetite, sometimes dyspnea. Some people may initially be suspected of hyperthyroidism. Diagnosis may also reveal an increased basal metabolism, which can be a sign of complications or the result of leukemic proliferation. 

 

2) Symptoms related to abnormal blood counts – Anemia and tendency to infections are generally rare during the first month of evolution because the white blood cells are functional. More often there is a tendency to hemorrhage [bleeding gum, epistaxis, purpura (red or purple discolorations on the skin)], bleeding during dental extractions). 


3) Symptoms related to the development of leukemic tissue:  

a) The spleen is enlarged (splenomegaly), and sometimes reaches the left iliac fossa. It is hard and painless unless there is the perisplenitis (inflammation of the tissues surrounding the spleen). In this case you may hear auscultation. Splenomegaly is often manifested and can be visible in the epigastrium or left upper quadrant. Sometimes severe pain can occur in patients who suffer from perisplenitis.
b) Lymph nodes are not enlarged in the majority of cases. But when lymphadenopathy (enlargement or infection
 of the lymph nodes) is present the condition is generally considered serious.
c) The liver is often slightly enlarged, at least, at the end.
d) The bones can be spontaneously painful, or when under pressure. 

 

Treatment of Chronic Myeloid Leukemia 

With very few exceptions, chronic myeloid leukemia remains incurable. Before the recent coming of targeted therapies, the median survival with conventional drugs like Misulban and Hydrea was 5 years, and the outcome was always fatal by transformation into acute leukemia. The treatment aims to delay the maximum acute transformation and control leukocytosis to prevent complications. 

 

A cure is possible after allogenic bone marrowtransplant from either family (siblings) or non-family donor for patients less than 50 years. Patients receive much longer remissions when treated with Interferon alpha. Several better chemotherapy drugs are also underway. Since the late 1990s, there is an emergence of new chemo drugs on the market: Gleevec, Sprycel or Tasigna, and others. Regarding Gleevec (Imatinib), it can radically transform the prognosis. This treatment recently puts on the market makes it possible to target cancer cells: chromosomal abnormality of CML causes a translocation between chromosomes 9 and 22 which allows the formation of a protein that has an aberrant tyrosine kinase activity… 

 

 

It is this activity that “instructs “cancer cells to grow out of control and prevents them from undergoing apoptosis (programmed cell death). Imatinib has an inhibitory action on the tyrosine kinase activity of Bcr-Abl (Bcr-Abltyrosine-kinase inhibitor) because it will bind to the binding site of adenosine triphosphate of the protein, preventing it from functioning properly to facilitate cancerous proliferation. It is a target therapy medication and now used in 1st line of chronic myeloid leukemia treatment.