Recent Developments in Chronic Myeloid Leukemia Biology and Treatment
Pp. 29-72 (44)
Massimiliano Bonifacio and Claudio Sorio
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.
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.
Section of Hematology, Department of Medicine, University of Verona, Italy.