Frequency and prognostic influence of ASXL1 mutations and its potential association with BCR-ABL1 transcript type and smoke in chronic myeloid leukemia patients.
Gene
; 886: 147776, 2023 Nov 30.
Article
en En
| MEDLINE
| ID: mdl-37689224
ABSTRACT
BACKGROUND:
Heterogeneous response to tyrosine kinase inhibitors (TKIs) and progress to advance phases, still is a significant clinical problem. These are attributed to additional mutations in mutated non-ABL1 genes. we aimed to determine prognostic effects of ASXL1 mutations as a biomarker for diverse treatment response and disease progression to aid clinical management.METHODS:
We performed ASXL1 gene mutational screening in 80 Ph+CML patients at different phases and 10 healthy control by direct sequencing method. Multiplex and qRT-PCR, standard chromosome banding analysis were used to determine BCR-ABL1 transcript type, molecular and cytogenetic responses respectively.RESULTS:
overall, four type mutations were identified in 11.25% of the patients. There was significant difference regarding mutation frequency between chronic and advance phases (P = 0.0002), sokal risk score (P = 0.0001), smoking (P = 0.02) and mean of during time of imatinib treatment (P = 0.009) between patients with and without ASXL1 mutations. ASXL1 mutations frequency had a bias toward younger than older and women than men, but no significant (P > 0.05). ASXL1 mutations were found more recurrently in patients carrying ABL1 KD mutations (P = 0.003). The risk of increasing resistance and disease progression in patients with ASXL1 mutations was 32 and 63 fold higher than those without mutations respectively (P = 0.01; P = 0.0002). The risk of ASXL1 mutations presence in patients with b2a2 transcript type was much higher than b3a2 type (P = 0.02, OR = 10).CONCLUSION:
Our findings suggest that ASXL1 mutations may be favorable predictive biomarkers to determine the best TKI for each patient, and to prevent CML progression.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Leucemia Mieloide
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Gene
Año:
2023
Tipo del documento:
Article