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.

Yi-Jiun Su ¹, Ming-Chung Kuo ¹ ², Tsai-Yun Chen ³, Ming-Chung Wang ⁴, Youngsen Yang ⁵ ⁶, Ming-Chun Ma ⁴, Tung-Liang Lin ¹, Tung-Huei Lin ¹, Hung Chang ¹, Chieh-Lin Jerry Teng ⁷ ⁸ ⁹, Pei-Ching Hsiao ¹⁰, Chih-Cheng Chen ² ¹¹, Po-Nan Wang ¹, Lee-Yung Shih ¹ ²

Affiliations

1 Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
2 Chang Gung University, School of Medicine, Taoyuan, Taiwan.
3 National Cheng Kung University Hospital, Tainan, Taiwan.
4 Division of Hematology-Oncology, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan.
5 Division of Hematology-Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
6 Internal Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
7 Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
8 Department of Life Science, Tunghai University, Taichung, Taiwan.
9 School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
10 Chung Shan Medical University Hospital, Taichung, Taiwan.
11 Division of Hematology-Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.

PMID: 35869805 DOI: 10.1111/cas.15501

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.

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