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INTRODUCTION

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SUMMARY

The chronic myelogenous leukemias (CMLs) include BCR rearrangement-positive CML, chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, and chronic basophilic leukemia. The term chronic, in contrast to acute, once had prognostic implications. However, although the terms remain useful for nosology, they no longer reflect an invariable difference in prognosis. For example, acute myelogenous leukemia in children and young adults has higher remission and cure rates than juvenile or chronic myelomonocytic leukemia in children or adults, respectively. BCR rearrangement-positive CML presents with anemia, exaggerated granulocytosis, a large proportion of myelocytes and mature neutrophils, absolute basophilia, normal or elevated platelet counts, and, frequently, splenomegaly. The marrow is intensely hypercellular, and marrow cells contain the Philadelphia (Ph) chromosome in approximately 90 percent of cases by cytogenetic analysis. A rearrangement of the BCR gene on chromosome 22 is present by molecular diagnostic analysis in approximately 96 percent of cases that have a classic morphologic appearance. The BCR-rearranged form of the disease usually responds to a tyrosine kinase inhibitor, and median survival has been extended significantly. Allogeneic hematopoietic stem cell transplantation can cure the disease, especially if the transplantation is applied early in the chronic phase, although this approach is now uncommon as a result of the effect of tyrosine kinase inhibitor therapy. The effect of stem cell transplantation is related in part to a robust graft-versus-leukemia effect, engendered by donor T lymphocytes. The natural history of the chronic phase is to evolve into an accelerated phase that often terminates in acute leukemia (blast crisis), but the frequency of this progression has been markedly decreased by the advent of tyrosine kinase inhibitors. Blast crisis results in a myelogenous leukemic phenotype in 75 percent of cases and a lymphoblastic leukemic phenotype in approximately 25 percent of cases. Ph chromosome–positive acute myeloblastic leukemia (AML) may appear de novo in approximately 1 percent of cases of AML, and Ph chromosome–positive acute lymphocytic leukemia (ALL) may occur de novo in approximately 20 percent of cases of adult ALL and approximately 5 percent of childhood ALL cases. In Ph chromosome–positive ALL, the translocation between chromosomes 9 and 22 results in the fusion gene encoding a mutant tyrosine kinase oncoprotein that may be identical in size to that in classic CML (210 kDa) in approximately one-third of cases. A smaller mutant tyrosine kinase (190 kDa) is encoded in approximately two-thirds of cases. In children, the cells in approximately 90 percent of cases contain a 190-kDa mutant tyrosine kinase. These acute leukemias may reflect (1) the presentation of CML in acute blastic transformation without a preceding chronic phase or (2) de novo cases resulting from a BCR-ABL1 mutation occurring in a different early hematopoietic cell from the event in CML or with as yet unidentified modifying gene alterations. Chronic myelomonocytic leukemia has variable presenting features. Anemia may be accompanied by mildly or moderately elevated leukocyte counts; an elevated total monocyte count; a low, normal, or elevated platelet ...

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