The Biology of Chronic Myelogenous Leukemia: Implications for Imatinib Therapy

Ricardo H. Alvarez, Hagop Kantarjian, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

Chronic myelogenous leukemia (CML) results from the neoplastic transformation of primitive hematopoietic stem cells, and has been classified as a myeloproliferative disorder. The hallmark of CML is the presence of a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11.2), which is known as the Philadelphia (Ph) chromosome. This translocation results in the formation of the bcr-abl fusion gene, which, in turn, is translated into a chimeric Bcr-Abl protein with deregulated tyrosine kinase activity. Constitutive Bcr-Abl expression has been shown to be necessary and sufficient for the transformed phenotype of CML cells. CML is unique among human cancers in that a single genetic defect, the Ph chromosome, is responsible for the transformed phenotype. Since this discovery more than 40 years ago, our understanding of the clinical course, therapy, and prognosis of patients with CML has changed significantly. These changes have culminated in the emergence of imatinib, the first rationally designed, molecularly targeted therapy for human malignancy. In this review, the authors describe the molecular biology of CML and the development of imatinib as a therapeutic agent for the treatment of CML.

Original languageEnglish (US)
Pages (from-to)4-14
Number of pages11
JournalSeminars in Hematology
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Therapeutics
abl Genes
Phenotype
Chromosomes, Human, Pair 22
Myeloproliferative Disorders
Chromosomes, Human, Pair 9
Hematopoietic Stem Cells
Imatinib Mesylate
Protein-Tyrosine Kinases
Molecular Biology
Neoplasms
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

The Biology of Chronic Myelogenous Leukemia : Implications for Imatinib Therapy. / Alvarez, Ricardo H.; Kantarjian, Hagop; Cortes, Jorge E.

In: Seminars in Hematology, Vol. 44, No. SUPPL. 1, 01.01.2007, p. 4-14.

Research output: Contribution to journalArticle

Alvarez, Ricardo H. ; Kantarjian, Hagop ; Cortes, Jorge E. / The Biology of Chronic Myelogenous Leukemia : Implications for Imatinib Therapy. In: Seminars in Hematology. 2007 ; Vol. 44, No. SUPPL. 1. pp. 4-14.
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