Management of chronic myeloid leukemia: targets for molecular therapy.

Abstract:

:Chronic myeloid leukemia (CML) is a hematopoietic disorder characterized by malignant expansion of bone marrow stem cells. Currently, the only unequivocally curative treatment for CML is allogeneic stem cell transplant. Unfortunately, a large proportion of CML patients are ineligible for such treatment and alternative forms of therapy must be employed. Conventional chemotherapy makes use of compounds, such as hydroxyurea, that are cytotoxic for actively dividing cells. Although effective, these agents are not selective for the leukemic clone and this is the cause of undesirable side effects. Moreover, as the disease progresses patients frequently become refractory to chemotherapy. In recent years, knowledge of the molecular pathology of CML has allowed the development of drugs that selectively target the malignant cells: imatinib mesylate is the most prominent example. These agents are selective because they target molecular determinants that are exclusively deregulated in the leukemic cells. In this review we consider some of the novel developments in this field. Particular emphasis is given to chemical agents that target the Bcr-Abl oncoprotein. The latter affords an excellent opportunity for therapy since CML, in contrast to many other human malignancies, is likely caused by the activity of a single oncoprotein. Furthermore, it is believed that Bcr-Abl continues to play a central role throughout the course of the disease.

journal_name

Semin Hematol

journal_title

Seminars in hematology

authors

Barnes DJ,Melo JV

doi

10.1053/shem.2003.50002

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

34-49

issue

1

eissn

0037-1963

issn

1532-8686

pii

S0037196302000045

journal_volume

40

pub_type

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