This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.
Download full-text PDF |
Source |
---|
Int J Mol Sci
December 2024
School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
The most frequent type of leukemia in Africa is chronic myeloid leukemia (CML). The genetic background of the rarer Philadelphia chromosome (Ph) Ph-ve (BCR-ABL-ve) subform of CML is largely unknown in African patients. Therefore, in this study, we aimed to investigate the role of CYP1A1 and 2D6 SNPs in the pathogenesis of Ph-ve CML in the Sudanese population.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Suite 523, Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
Overexpression of the myeloid Src-family kinases Fgr and Hck has been linked to the development of acute myeloid leukemia (AML). Here we characterized the contribution of active forms of these kinases to AML cell cytokine dependence, inhibitor sensitivity, and AML cell engraftment in vivo. The human TF-1 erythroleukemia cell line was used as a model system as it does not express endogenous Hck or Fgr.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Blood Disease Institute, Xuzhou Medical University,Xuzhou 221000, Jiangsu Province, China.
Malays J Pathol
December 2024
National Institutes of Health, Institute for Medical Research, Cancer Research Centre, Haematology Unit, 40170 Shah Alam, Selangor, Malaysia.
Introduction: The emergence of mutations in the BCR::ABL1 kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contributing to IM resistance. Identification of these mutations is important for treatment decisions and precision medicine in chronic myeloid leukaemia (CML) patients. Our study aims to determine the frequency of BCR::ABL1 KD mutations in CML patients with IM resistance.
View Article and Find Full Text PDFAdv Lab Med
December 2024
Department of Clinical Haematology, National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan.
Objectives: kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival.
Methods: Patients with a response which categorized them into warning zone/or who failed to respond to their TKI treatment completely as per the European LeukemiaNet (ELN) were labeled as non-responders.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!