Chronic Granulocytic Leukemia

Abstract

Abstract Chronic granulocytic leukemia is a clonal stem cell disorder characterized by the t(9;22) translocation, predominant proliferation of differentiated granulocytes during the chronic phase, and biphasic clinical course. Chronic granulocytic leukemia (CGL) is a stem cell disorder with predominant proliferation of differentiated granulocytes. Chronic granulocytic leukemia has been epitomized as the disease of one million: one million white blood cells, one million platelets, and one million red blood cells indicating the cardinal findings of leukocytosis, thrombocytosis, and anemia. Chronic granulocytic leukemia is associated with a characteristic cytogenetic abnormality, the t(9,22) translocation, known as the Philadelphia chromosome (Nowell and Hungerford, 1960). The Philadelphia chromosome is found in immature granulocytes, erythroid cells, megakaryocytes, and some B lymphocytes in patients with chronic granulocytic leukemia, indicating a stem cell origin (Fialkow et al, 1977). The Philadelphia chromosome is characterized by rearrangement of the c-abl protooncogene on chromosome 9 with a protein gene in the breakpoint cluster region of chromosome 22. The resultant fusion gene, bcr-abl, is a major factor in the pathogenesis of chronic granulocytic leukemia and is necessary and sufficient for the CGL phenotype. The human bcr-abl gene has been cloned and insertion of the cloned gene into mouse hematopoietic cells results in a disorder resembling human chronic granulocytic leukemia (Daley et al, 1990).