Prognostic Significance of Transcript-Type BCR - ABL1 in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL1 fusion gene. In more than 95% of CML patients, the typical BCR-ABL1 transcript subtypes are e13a2 (b2a2), e14a2 (b3a2), or the simultaneous expression of both. Other less frequent transcript subtypes, such as e1a2, e2a2, e6a2, e19a2, e1a3, e13a3, and e14a3, have been sporadically reported. The main purpose of this review is to assess the possible impact of different transcripts on the response rate to tyrosine kinase inhibitors (TKIs), the achievement of stable deep molecular responses (s-DMR), the potential maintenance of treatment-free remission (TFR), and long-term outcome of CML patients treated with TKIs. According to the majority of published studies, patients with e13a2 transcript treated with imatinib have lower and slower cytogenetic and molecular responses than those with e14a2 transcript. They should be considered a high-risk group that would most benefit from frontline treatment with second-generation TKIs (2GTIKIs). Although few studies have been published, similar significant differences in response rates to 2GTKIs have been not reported. The e14a2 transcript seems to be a favorable prognostic factor for obtaining s-DMR, irrespective of the TKI received, and is also associated with a very high rate of TFR maintenance. Indeed, patients with e13a2 transcript achieve a lower rate of s-DMR and experience a higher probability of TFR failure. According to most reported data in the literature, the type of transcript does not seem to affect long-term outcomes of CML patients treated with TKIs. In TFR, the e14a2 transcript appears to be related to favorable responses. 2GTKIs as frontline therapy might be a convenient approach in patients with e13a2 transcript to achieve optimal long-term outcomes.