Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia
Hematol., Transfus. Cell Ther. (Impr.)
; 40(4): 363-367, Oct.-Dec. 2018. graf, ilus
Article
en En
| LILACS
| ID: biblio-984503
Biblioteca responsable:
BR408.1
Ubicación: BR408.1
ABSTRACT
ABSTRACT Introduction:
Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance.Objective:
To evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná.Methods:
This retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing.Results:
Sixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I).Conclusions:
This molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
LILACS
Asunto principal:
Virus de la Leucemia Murina de Abelson
/
Proteínas Tirosina Quinasas
/
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Proteínas Proto-Oncogénicas c-bcr
/
Mutación
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Hematol., Transfus. Cell Ther. (Impr.)
Asunto de la revista:
Hematologia
/
TransfusÆo de Sangue
Año:
2018
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Brasil