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- Title
Imatinib and tyrosine kinase inhibition, in the management of BCR-ABL negative myeloproliferative disorders.
- Authors
Mesa, Ruben A.
- Abstract
The chronic myeloproliferative disorders (MPDs) include the spectrum of clonal hematopoietic stem cell disorders whose phenotype derive from the primary cell expanded in a proliferative state. The MPDs (which include polycythemia vera (PV), essential thrombocythemia (ET), chronic eosinophilic leukemia (CEL), primary myelofi brosis (PMF), chronic myelomonocytic leukemia (CMML), and systemic mast cell disease (SMCD)) exclude chronic myeloid leukemia (CML) because of the pathognomic importance of the BCR-ABL translocation for the diagnosis and treatment of this disorder with imatinib mesylate. Empiric use of imatinib mesylate against the spectrum of BCR-ABL negative MPDs has had mixed results. Signifi cant benefi ts were obtained when empiric use of imatinib in CEL and CMML led to signifi cant clinical benefit and the discovery of the role of rearrangements of the platelet derived growth factor receptor -alpha (PDGFRa-FIP1L1 in CEL and SMCD) and -beta (PDGFRb through TEL-PDGFRb) for CMML). Empiric use of imatinib in PMF has been disappointing, and in PV quite modest. Although next generation Abelson kinase inhibitors such as dasatinib or nilotinib may expand the role for these agents in MPDs, targeted inhibition of the mutant kinase JAK2V617F is more likely to make significant therapeutic gains in the classic MPDs of PV, ET, and PMF.
- Publication
Biologics: Targets & Therapy, 2007, Vol 1, Issue 2, p129
- ISSN
1177-5475
- Publication type
Article