Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ INTRODUCTION ++ BCR-ABL-positive chronic myelogenous leukemia (CML) results from a somatic mutation in a pluripotential lymphohematopoietic cell. CML is characterized by granulocytic leukocytosis, granulocytic immaturity, basophilia, anemia, and often thrombocytosis in the blood, intense leukemic granulocytic precursor expansion in the marrow, and splenomegaly. The natural history of the disease is to evolve into an accelerated phase in which cytopenias develop and response to chronic phase therapy is lost; it often terminates in acute leukemia. ++ ETIOLOGY ++ Exposure to high-dose ionizing radiation increases the incidence of CML, with a mode of increased incidence that ranges from 4 to 11 years in different exposed populations. ++ PATHOGENESIS ++ Genetic Abnormality ++ CML is the result of an acquired genetic abnormality that induces a malignant transformation of a single pluripotential lymphohematopoietic cell. The proximate cause is a translocation between chromosome 9 and 22 [t(9;22)]. This alteration juxtaposes a portion of the ABL protooncogene from chromosome 9 to a portion of the BCR gene on chromosome 22. The resulting gene fusion, BCR-ABL, creates an oncogene that encodes an elongated protein tyrosine phosphokinase (usually p210) that is constitutively expressed. This mutant protein disrupts cell signal pathways and results in the malignant transformation. The genetic alteration is present in erythroid, neutrophilic, eosinophilic, basophilic, monocytic, megakaryocytic, and marrow B- and T-lymphocytic cells, consistent with its origin in a pluripotential cell. The Philadelphia (Ph) chromosome specifically refers to chromosome 22 with a shortened long arm and is evident by light microscopy of cell metaphase preparations in approximately 90 percent of cases. Fluorescence in situ hybridization (FISH) can identify the fusion BCR-ABL gene in approximately 95 percent of cases. ++ Hematopoietic Abnormalities ++ There is a marked expansion of granulocytic progenitors and a decreased sensitivity of the progenitors to regulation resulting in an inexorable increase in white cell count. Megakaryocytopoiesis is often expanded. Erythropoiesis is usually moderately deficient. Function of the neutrophils and platelets is nearly normal; infection and bleeding are not a feature of the chronic phase. ++ EPIDEMIOLOGY ++ CML accounts for approximately 15 percent of all cases of leukemia and approximately 3 percent of childhood leukemias. Males are affected at approximately 1.5 times the rate of females. The age-specific incidence rate increases exponentially from late teen age (0.2 cases/100,000) to octogenarians (10 cases/100,000). Familial occurrence is vanishingly rare, and there is no concordance in identical twins. Neither chemical agents, including benzene, cytotoxic drugs, nor combusted tobacco smoke have a causal relationship with CML. ++ CLINICAL FEATURES ++ Approximately 30 percent of patients are asymptomatic at the time of diagnosis. The disease is discovered coincidentally when an elevated white count is noted at a medical evaluation. Symptoms are gradual in onset and may include easy fatigability, malaise, anorexia, abdominal discomfort and early satiety, weight loss, and excessive sweating. Less frequent symptoms ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!