Abstract
The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.
Highlights
Chronic myeloid leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene
We studied 202 chronic myeloid leukemia (CML) patients from seven Spanish centers diagnosed from 1999 to 2016, most of them with a minimum follow-up of 18 months on IM treatment
All patients were treated with IM at standard doses as first-line tyrosine–kinase inhibitor (TKI) therapy
Summary
Chronic myeloid leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene. The most frequent breakpoint of chromosome 22, known as the major breakpoint cluster region (M-bcr), comprises exon 13 or exon 14, generating the e13a2 (b2a2) or the e14a2 (b3a2) transcripts. Both are translated into a constitutively active protein of 210 kDa that differs in 25 amino acids more from the e14a2 transcript [1,2,3]. In some nonresistant patients, minimal residual disease persists during TKI therapy. In the IM era, a Brazilian study, including a small number of patients at different phases of the disease, suggested that patients with the e13a2 transcript were more sensitive to IM in terms of molecular response [9], whereas other studies with larger number of patients demonstrated a better molecular response to IM in patients with the e14a2 transcript [3,10,11,12]
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