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Molecular Biology of Chronic Myeloid Leukemia

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Abstract

Multistep carcinogenesis is exemplified by chronic myeloid leukemia with clinical manifestation consisting of a chronic phase and blast crisis. Pathological generation of BCR-ABL (breakpoint cluster region-Abelson) results in growth promotion, differentiation, resistance to apoptosis, and defect in DNA repair in targeted blood cells. Domains in BCR and ABL sequences work in concert to elicit a variety of leukemogenic signals including Ras, STAT5 (signal transducer and activator of transcription-5), Myc, cyclin D1, PI3 (phosphatidylinositol 3-kinase), RIN1 (Ras interaction/interference), and activation of actin cytoskeleton. However, the mechanism of differentiation of transformed cells is poorly understood. A mutator phenotype of BCR-ABL could explain the transformation to blast crisis.The aim of this review is to integrate molecular and biological information on BCR, ABL, and BCR-ABL and to focus on how signaling from those molecules mirrors the biological phenotypes of chronic myeloid leukemia.

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    Yoshiro Maru

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Maru, Y. Molecular Biology of Chronic Myeloid Leukemia. Int J Hematol 73, 308–322 (2001). https://doi.org/10.1007/BF02981955

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