Frontiers in Clinical Drug Research: Hematology

Frontiers in Clinical Drug Research: Hematology

Volume: 3

Frontiers in Clinical Drug Research – Hematology is a book series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the ...
[view complete introduction]

US $
30

*(Excluding Mailing and Handling)



Recent Developments in Chronic Myeloid Leukemia Biology and Treatment

Pp. 29-72 (44)

Massimiliano Bonifacio and Claudio Sorio

Abstract

BCR-ABL1 represents a driving force in the biology of CML cell as demonstrated by the spectacular results of tyrosine kinase inhibitor (TKI) therapies. Imatinib is a highly effective therapy for chronic phase-chronic myeloid leukaemia (CP-CML) patients, as it turned CML blastic transformation into a rare event. However, responses to frontline imatinib are variable and 2nd- (nilotinib, dasatinib and bosutinib) or 3rd-generation (ponatinib) TKIs have been developed to face BCR-ABL1 mutation-induced imatinib resistance, or intolerance. Nilotinib and dasatinib have been licensed also for the frontline treatment of newly diagnosed patients and they proved to be more effective than imatinib in inducing earlier and deeper molecular responses. However, the reappearance of leukemic cells after TKI discontinuation also in patients with stable negative minimal residual disease highlighted the concept of persistence of BCR-ABL1 leukemia stem cells. Data have accumulated in the past years that the BCR-ABL1 oncogene does not operate alone to drive disease emergence, maintenance and progression: These issues will be briefly reviewed with a special focus on the emerging role of phosphatases in the pathogenesis of hematologic malignancies as new therapeutic approaches have been proposed based on findings in basic science laboratories. Critical issues and future trends will be discussed including the need to better characterize patients according to prognostic scores, paying more attention to those at high risk for disease progression, the increased importance of early monitoring and the optimization of treatment in order to provide an “operational cure” (discontinuation of treatment) in a considerable proportion of patients.

Keywords:

BCR-ABL1 mutations, Bosutinib, Chronic myeloid leukemia, Dasatinib, Early molecular response, Imatinib, Leukemia, Minimal residual disease, Nilotinib, Phosphatases, Ponatinib, Quality of life, Treatment free remission, Tyrosine kinase inhibitors.

Affiliation:

Section of Hematology, Department of Medicine, University of Verona, Italy.