Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: study by the Nagasaki CML Study Group.
نویسندگان
چکیده
An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment.
منابع مشابه
The prognostic relevance of BCR-ABL1 transcript type, Sokal score and smoke as synergestic factor with complete cytogenetic response in CML patients treated with different TKI modalities
Background: In chronic myeloid leukemia (CML), the influence of BCR-ABL1 transcript type, Sokal risk score and smoke on disease phynotype and cytogenetic response to treatment is still unknown and arguable. The objective of this study was to determine the prognostic significance of transcript types, risk score and smoking status among patients with CML treated with different tyrosine kinase inh...
متن کاملSignaling pathways involved in chronic myeloid leukemia pathogenesis: the importance of targeting Musashi2-Numb signaling to eradicate leukemia stem cells
Objective(s): Chronic myeloid leukemia (CML) is a myeloid clonal proliferation disease defining by the presence of the Philadelphia chromosome that shows the movement of BCR-ABL1. In this study, the critical role of the Musashi2-Numb axis in determining cell fate and relationship of the axis to important signaling pathways such as Hedgehog and Notch that are essential ...
متن کاملStudy of STAT3 Expression in Different Phases of Patients with Chronic Myeloid Leukemia
Background and Aim: Chronic myeloid leukemia(CML) is a clonal myeloproliferative disease, characterized by BCR/ABL translocation. Using tyrosine kinase inhibitors such as Imatinib, treatment for this disease has progressed remarkably. However, resistance to tyrosine kinase inhibitor is a major obstacle. Signal transducer and activator of transcription 3(STAT3) is an important transcription fact...
متن کاملPonatinib in refractory Philadelphia chromosome-positive leukemias.
BACKGROUND Resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) is frequently caused by mutations in the BCR-ABL kinase domain. Ponatinib (AP24534) is a potent oral tyrosine kinase inhibitor that blocks native and mutated BCR-ABL, including the gatekeeper mutant T315I, which i...
متن کاملMolecular biology of bcr-abl1-positive chronic myeloid leukemia.
Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In re...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Leukemia research
دوره 38 1 شماره
صفحات -
تاریخ انتشار 2014