Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia.

Abstract:

:Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib resistance in patients with chronic myeloid leukemia (CML). Here we examine predisposing factors underlying acquisition of KD mutations, evidence for acquisition of mutations before and during therapy, and whether the detection of a KD mutation universally implies resistance. We also provide a perspective on how the second-line Abl inhibitors dasatinib and nilotinib are faring in the treatment of imatinib-resistant CML, especially in relation to specific KD mutations. We discuss the growing importance of the multi-inhibitor-resistant 315T>I mutant and the therapeutic potential that a 315T>I inhibitor would have. Last, we assess the potential of Abl kinase inhibitor combinations to induce stable responses even in advanced CML and interpret the emerging data in the context of CML pathogenesis.

journal_name

Blood

journal_title

Blood

authors

O'Hare T,Eide CA,Deininger MW

doi

10.1182/blood-2007-03-066936

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

2242-9

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2007-03-066936

journal_volume

110

pub_type

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