Michael Deininger

Chronic myeloid leukemia (CML) is probably the most extensively studied malignancy and has served as a pacemaker for the development of new concepts and strategies in oncology. It was the description of the first CML cases, independently by Bennet1 and Virchow,2 which led to the term "leukemia," Greek for "white blood." CML was the first human cancer consistently associated with a chromosomal abnormality, the Philadelphia (Ph) chromosome.3 It was also the first malignancy that was faithfully reproduced in an animal model based on precise knowledge of the causal molecular lesion.4 Lastly, CML was the first malignant condition, where the identification of the causal abnormality led to a specific therapy.5 Despite intensive efforts, important aspects of CML pathogen-esis are not well understood, such as the mechanisms underlying the progression to blast crisis. This chapter reviews the pathogenesis of CML, with a slight emphasis on clinical applications. Due to the wealth of data, this review cannot be comprehensive, and many important aspects had to be omitted because of space constraints.

the peripheral blood. Megakaryocytes are frequently increased in numbers, tend to be small and hypolobu-lated (micromegakaryocytes), and form clusters or sheets. Other findings include pseudo-Gaucher cells or sea-blue histiocytes, both representing macrophages that are unable to metabolize the increased glucocere-broside load associated with the high cell turnover. Bone marrow histology yields additional information and is mandatory in the case of a "dry tap," as it may reveal increased blasts that are not apparent on the blood smear. Various degrees of reticulin fibrosis are a common finding, particularly in patients with more advanced disease.8 Angiogenesis is also increased but vessel density is not part of standard histologic reports, since it requires special stains.9 Overall, the morphologic findings allow establishing the diagnosis of a myeloproliferative syndrome, consistent with CML. However, a definitive diagnosis of CML should be made only after the presence of the Ph chromosome, or the BCR-ABL translocation has been documented by cytogenetic or molecular techniques (see below).

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