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INTERNATIONAL CONGRESS OF

CancerGenetics

• Frequency and prognostic influence of ASXL1 mutations and its potential association with BCR-ABL1 transcript type and smoke in chronic myeloid leukemia patients

• Mohammad Hamid,^1,* Golale rostami,² Aras Rafiq Mohammed,³ Dlnya Assad,⁴
  1. Pasteur Institute of Iran
  2. Pasteur Institute of Iran (IPI),No. 69,Pasteur Ave, Tehran, Iran.
  3. Department of Biology, College of Science, Sulaimani University, Sulaymanyah, Iraq
  4. Department of Biology, College of Science, Sulaimani University, Sulaymanyah, Iraq
  
  
  
• Introduction: 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.
• Keywords: ASXL1 Chronic myeloid leukemia Mutations Resistance Smoke