How to detect the rare BCR‑ABL (e14a3) transcript: A case report and literature review

Abstract

Abstract. The Philadelphia (Ph; BCR-ABL) chromosome originates from a translocation event between chromosomes 9 and 22, and results in the BCR-ABL fusion gene. In chronic myelogenous leukemia (CML), the BCR-ABL gene is mainly coded for by a major breakpoint cluster region (M-bcr, e13a2 and e14a2). However, in some patients, BCR-ABL genes are encoded by a minor (m)-bcr, e1a2, and a micro (µ)-bcr region, e19a2. These transcripts revealed a different clinical course. The present study described a CML patient whose cytogenetics and FISH analyses of bone marrow revealed a karyotype of 46, XY t(9,22) (q34;q11), while the commercial kits of quantitative PCR (qPCR) failed to detect the BCR-ABL fusion gene. Further multiplex Reverse transcription-PCR (RT-PCR) and sequencing analyses identified a rare e14a3 (b3a3) fusion transcript.

Rapid decline of Philadelphia‑positive metaphases after nilotinib treatment in a cml patient expressing a rare e14a3 bcr‑abl1 fusion transcript: A case report

“…We therefore decided to employ primers recognizing more distant exons from the common BCR-ABL1 breakpoints and successfully identified the atypical BCR-ABL1 e14a3 rearrangement. To date, different cases of CML patients expressing this isoform have been reported (16,21,23,24). Although IM represents an excellent first line therapy for most CML patients (7), extensive published data suggest that patients receiving this drug may more frequently develop both BCR-ABL-dependent and BCR-ABL-independent resistance to therapy (8,19,25) requiring alternative treatments (26).…”

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

“…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. To the best of our knowledge, 19 CML patients (including our patient) have been reported with the e14a3 fusion, and the information is summarized in Table 2 (part of the case report references are quoted and obtained from two of the former studies 48,49 ). The e14a3 fusion was found to be common in men, and patients with e14a3 transcript were younger than those with typical transcripts at diagnosis.…”

Chronic Myeloid Leukemia with b3a3 (e14a3) Fusion: A Rare BCR/ABL Rearrangement Presenting with Thrombocytosis – Does MTHFR Polymorphism Matter

“…Fifteen cases of CML with the e14a3 transcript has been reported to the best of our knowledge (Table 1 ) and due to the limited number of cases, the clinical characteristics and prognostic outcomes to therapy are difficult to define[ 7 , 8 ]. White blood cell counts in these patients range from 9 to 300 × 10 9 /L and 6 out of 10 patients exhibited some degree of thrombocytosis; however, none of the previously reported patients exhibited such a marked degree of thrombocytosis as the patient in our case report.…”

“… INF, interferon therapy; Hu, hydroxyurea; ABMT, autologous bone marrow transplantation; mo, months. Individual case report references and table adapted from Table 1 from Hu et al [ 8 ]. …”