Clinical characteristics and prognostic significance of chronic myeloid leukemia with rare BCR-ABL1 transcripts

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

“…The presence of e1a2 transcript (encoding for p190) is associated with higher risk of disease progression and inferior cytogenetic and molecular responses to TKI therapy. [22][23][24][25][26] In multivariate analysis, e1a2 transcript was also identified as an independent predictor of inferior survival outcomes. 24 It is important to be aware that these data refer to the presence of dominant e1a2 transcript, not to the presence of low-level e1a2 transcripts in patients with dominant e13a2 or e14a2 transcripts.…”

“…The presence of e19a2 transcript (encoding for p230) is associated with lower rates of cytogenetic and molecular response to TKIs and inferior survival outcomes, despite previous reports of an indolent disease course in the pre-TKI era. [25][26][27] Referral to centers with expertise in the management of CML is recommended.…”

Breakpoint mapping of a t(9;22;12) chronic myeloid leukaemia patient with e14a3 BCR‐ABL1 transcript using Nanopore sequencing

“…In rare cases, the breakpoints are located outside the above three regions, which form the atypical fusion transcripts, such as e19a2, e1a2, e8a2, e6a2, e12a2, e13a3, e14a3 and e1a3, and so on 47 . Among these rare transcript types, the frequency of e14a3 in overall CML patients was described in the range from 0.2% to 0.3% according to previous large sample studies 17–19 . Although three important recommended methods (cytogenetics, FISH and RT‐PCR) have been applied for the initial CML diagnosis, absence an of a commercial RT‐PCR kit with customized primers might have resulted in the omission of a number of detections in the past.…”

“…Based on the above cases, we may be able to roughly delineate that approximately half of the CML patients with e14a3 transcripts would benefit from imatinib. Furthermore, two recent retrospective analyses stated that patients with e13a3/e14a3 transcript had better outcomes upon imatinib treatment compared to those with the typical e13a2/e14a2 transcripts 18,19 …”

“…Although several studies had reviewed and concluded the features and prognosis of additional aberrations, 12–15 variant sequencing and breakpoint mapping have remained under studied. This is also true of reports concerning rare BCR‐ABL1 fusion transcripts 16–19 . Thus, researchers have focused on next‐generation sequencing (NGS), which has become an important tool for characterizing the structural variants (SVs) 20,21 .…”