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.