Response to Imatinib therapy is inferior for e13a2 BCR-ABL1 transcript type in comparison to e14a2 transcript type in chronic myeloid leukaemia.

Abstract

Background: The BCR-ABL1 fusion gene underlying the pathogenesis of CML can arise from a variety of breakpoints. The e13a2 and e14a2 transcripts formed by breakpoints occurring around exon 13 and exon 14 of the BCR gene respectively are the most common.

Methods: We undertook a retrospective audit using local laboratory database and electronic patient care records of 69 CML patients with an e13a2 or e14a2 transcript type identified in our regional population.

Results: The e13a2 group was on average significantly younger (45.0 years v 54.5 years), had a higher average white cell count (189.8 × 10⁹/l v 92.40 × 10⁹/l) and lower platelet count (308 × 10⁹/l v 644 × 10⁹/l) in comparison to the e14a2 group suggesting that these are distinct biological entities. Over an average follow-up of 33.8 months and 27.2 months for the e13a2 and e14a2 groups we observed an inferior molecular response to imatinib in the e13a2 group. A significantly lower number of patients in the e13a2 arm met European Leukemia Net criteria for optimal response at 12 months therapy (17.64% v 50.0%) and were slower to obtain deep molecular responses MR⁴ or MR^4.5.

Conclusion: Patients with an e13a2 transcript demonstrate an inferior molecular response to imatinib in our regional population.