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Chronic Myelocytic Leukemia (CML) (also known as chronic granulocytic leukemia-CGL)


Ionizing radiation appears to play an important role in the development of CML. This is well demonstrated with the effect of the atomic bomb in Hiroshima, in which there was a significant increase in the occurrence of CML. Most Common Clinical Features A. B. C. D. E. F. Splenomegaly Sternal Tenderness Slightly more common in men Usually occurs between ages of 20 and 60 Insidious onset Abnormal proliferation of granulocytic cells in the Bone Marrow and at extramedullary sites.



Laboratory Features A. B. C. D. E. F. G. Increased WBC count. Counts over 100,000 are not uncommon. No leukemic hiatus Myeloblasts and Promyelocytes generally make up less than 10% of the cell population. Usually an increase seen in basophils and eosinophils Pseudo Pelger-Huet Phenomenon may occur Mild Normocytic, Normochromic anemia may be present by time of diagnosis Platelets usually normal or increased/macroplatelets may be seen. (Thrombocytopenia may occur later in the disease due to impaired production and/or increased pooling of platelets in the enlarged spleen) Bone marrow is grossly hypercellular with very little fat space remaining/ M:E ratio greatly increased. Cytochemically, CML demonstrates a decreased leukocyte alkaline phosphatase (LAP) score

H. I.



In 1960, two physicians studying chromosomes in cancer cells noticed that one chromosome in cells from patients with CML (chromosome 22) was shorter than the same chromosome in normal cells. They named this shortened chromosome 22 the Philadelphia chromosome, because the observation was made in Philadelphia at the University of Pennsylvania School of Medicine. It is now referred to as the Ph chromosome. Thus, CML is distinguished from other leukemias by the presence of a genetic abnormality of chromosome 22 in leukemic cells. Normal human cells have 46 chromosomes, composed of 22 pairs of chromosomes and two sex chromosomes. The first 22 pairs (numbered 1 through 22) are called autosomes. The 45th and 46th chromosomes consist of sex determining chromosomes, either XY in males or XX in females. Further studies established that two chromosomes, usually chromosomes number 9 and 22, were abnormal. Pieces of the chromosomes, which are broken off in the leukemic cells of patients with CML, switch with each other. The detached portion of chromosome 9 sticks to the broken end of chromosome 22, and the detached portion of chromosome 22 sticks to the broken end of chromosome 9. This abnormal exchange of parts of chromosomes is called a translocation. This translocation of chromosome pieces occurs only in the damaged stem cell and in the various blood cells derived from that stem cell. The chromosomes of the cells in other tissues are normal. The breakage on chromosome 9 disrupts a gene referred to as ABL (for Abelson, the scientist who first described this gene). The breakage on chromosome 22 involves a gene referred to as BCR (for breakpoint cluster region). The human ABL gene is mutated by the breakage of chromosome 9. The mutated gene is translocated to chromosome 22 and fuses with the remaining part of the BCR gene. This fusion between BCR and ABL leads to an abnormal fused gene, called BCR-ABL. The function of a gene is to direct the production of a protein in the cell. In CML, the ABL gene fuses to the BCR gene, resulting in the production of an elongated enzyme protein called tyrosine kinase. This elongated protein functions abnormally and leads to dysfunctional regulation of cell growth and survival. The abnormal protein resulting from the mutant BCR-ABL gene is responsible for the development of the disease. Tyrosine kinase is a target for specific drug treatment that may block its effects. The cause of the chromosomal breakage, occurring in nearly all CML patients, is not known, for the most part. However, in a small number of patients, exposure to very high doses of radiation causes the breakage. This effect has been most carefully studied in the Japanese survivors of the atomic bomb, whose future risk of developing leukemia was significantly increased. A slight increase in risk also occurs in some individuals treated with highdose radiotherapy for other cancers, such as lymphoma. Exposures to diagnostic dental or medical x-rays have not been associated with an increased risk of CML. (From Chronic Myelogenous Leukemia, 2006, The Leukemia and Lymphoma Society). The University of MS Medical Center, and many other large hospitals, no longer use the LAP as the primary test for the evaluation of suspected Chronic Myelogenous Leukemia. The LAP test may suffer from high rates of false positives, low accuracy, and inter-technician interpretation

variability. The test of choice now offered for the screening for CML is the Fluorescence in Situ Hybridization, or FISH. It may be performed on either bone marrow or peripheral blood, and offers nearly 100% sensitivity. (See Chronic Myelogenous Leukemia, 2006, The Leukemia and Lymphoma Society, pages 11-12). For further information, click here. A. Philadelphia (Ph1) chromosome: translocation of part of chromosome #22 to chromosome #9 B. Abnormality is acquired, not inherited C. Seen in approximately 90% of patients with CML D. Generally, patients without the Philadelphia chromosome do not respond as well to therapy and have a shorter survival rate. Cause of Death: The primary cause of death is the conversion of CML into an AML-like blood picture, which is referred to as a blast crisis. The result is a leukemic infiltration of various organs. Course and Management: A. B. Single drug therapy is used. Bisulfan. Drug of choice is usually



Aim of Treatment: 1) lower the circulating WBC count 2) reduce the thrombocytosis 3) reduce the splenomegaly Prognosis 1) median survival 4 years 2) Blast Crises: In the advanced stages of be an increased number of peripheral blood and bone the blood picture seen in 3) the disease there may blasts in the marrow. May resemble subacute myelogenous leukemia.


death results from infection, hemorrhages, or organ infiltration with leukemic cells.

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