PURPOSE OF REVIEW: The successful introduction of the tyrosine kinase inhibitors has initiated a new era in the management of chronic myeloid leukemia. RECENT FINDINGS: Imatinib therapy has significantly improved prognosis of chronic myeloid leukemia. A minority of patients with chronic-phase disease (4% annually) and considerably more in advanced stages develop resistance. This is attributed, in 40-50% of cases, to the development of BCR-ABL (breakpoint cluster region/Abelson oncogene) tyrosine kinase domain mutations that impair imatinib binding. This has led to the development of more potent novel tyrosine kinase inhibitors that can overcome both BCR-ABL-dependent and BCR-ABL-independent mechanisms of resistance. Preliminary results of phase I and II trials with dasatinib and nilotinib have provided promising data that may reduce disease progression and potentially prevent acquired resistance to the tyrosine kinase inhibitors. SUMMARY: Novel tyrosine kinase inhibitors with more potent and selective Bcr-Abl inhibition and with multitargeted inhibition of Bcr-Abl and Src family kinases are promising and may further improve prognosis in chronic myeloid leukemia.
PURPOSE OF REVIEW: The successful introduction of the tyrosine kinase inhibitors has initiated a new era in the management of chronic myeloid leukemia. RECENT FINDINGS:Imatinib therapy has significantly improved prognosis of chronic myeloid leukemia. A minority of patients with chronic-phase disease (4% annually) and considerably more in advanced stages develop resistance. This is attributed, in 40-50% of cases, to the development of BCR-ABL (breakpoint cluster region/Abelson oncogene) tyrosine kinase domain mutations that impair imatinib binding. This has led to the development of more potent novel tyrosine kinase inhibitors that can overcome both BCR-ABL-dependent and BCR-ABL-independent mechanisms of resistance. Preliminary results of phase I and II trials with dasatinib and nilotinib have provided promising data that may reduce disease progression and potentially prevent acquired resistance to the tyrosine kinase inhibitors. SUMMARY: Novel tyrosine kinase inhibitors with more potent and selective Bcr-Abl inhibition and with multitargeted inhibition of Bcr-Abl and Src family kinases are promising and may further improve prognosis in chronic myeloid leukemia.
Authors: Roxana E Iacob; Teodora Pene-Dumitrescu; Jianming Zhang; Nathanael S Gray; Thomas E Smithgall; John R Engen Journal: Proc Natl Acad Sci U S A Date: 2009-01-21 Impact factor: 11.205