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BCR-ABL kinase domain mutations in CML patients, experience from a tertiary care center in North India.
S, Akhilesh; Shah, Arunim; Ashish, Ashish; Kumar Singh, Nitish; Kaur, Manpreet; Kumar Yadav, Abhay; Singh, Royana.
Afiliación
  • S A; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
  • Shah A; SCRC, SGPGIMS, Lucknow, India.
  • Ashish A; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
  • Kumar Singh N; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
  • Kaur M; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
  • Kumar Yadav A; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
  • Singh R; MRU Lab-Dept. of Anatomy, IMS, BHU, Varanasi, India.
Leuk Res Rep ; 21: 100403, 2024.
Article en En | MEDLINE | ID: mdl-39035746
ABSTRACT

Background:

Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCRABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCRABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India.

Methods:

In this study, the patient resistance for the imatinib were analyzed for BCRABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported.

Results:

329 patients with CML-CP were analyzed for BCRABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCRABL conferring resistance to different generations of TKI. Mutations in BCRABL kinase domain was observed in different domain of BCRABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %).

Conclusion:

Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leuk Res Rep Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leuk Res Rep Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido