LA LEUCÉMIE MYÉLOÏDE CHRONIQUE ET LES INHIBITEURS DE TYROSINE KINASE

Abstract

Chronic myeloid leukemia is a hematological malignancy in the group of myeloproliferative syndromes. It is characterized by the presence of an acquired genetic abnormality at the hematopoietic stem cells, the Philadelphia chromosome. Inhibitors of tyrosine kinase, whose leader is imatinib, has profoundly changed the therapeutic management and prognosis of this malignancy. The failure of imatinib treatment is due to resistance mechanisms that are not all fully characterized. However, cross and multiple resistance remain difficult to treat and require a better understanding of their mechanisms to overcome residual disease in the near future. The persistence of a long term residual disease associated with the presence of quiescent leukemic cells, and the occurrence of relapse led to the development of second and third generation inhibitors tyrosine kinase and the combination of these inhibitors with therapeutic immunomodulators such as interferon α, or vaccination protocols are discussed. The purpose of this review is to update on the molecular abnormalities found in chronic myeloid leukemia with emphasis on mechanisms of imatinib resistance and the current therapeutic strategy in the era of new generations of inhibitors of tyrosine kinase.