Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia

Cancer Sci. 2022 Oct;113(10):3518-3527. doi: 10.1111/cas.15501. Epub 2022 Aug 17.

Abstract

Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.

Keywords: chronic myeloid leukemia; molecular response; survival; transcript; tyrosine kinase inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Dasatinib / therapeutic use
  • Fusion Proteins, bcr-abl* / genetics
  • Humans
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Dasatinib