A variant transcript, e1a3, of the minor BCR–ABL fusion gene in acute lymphoblastic leukemia: case report and review of the literature

Abstract

We report a rare case of adult Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with an e1a3 fusion transcript. A 25-year-old female consulted our hospital for leukocytosis and thrombocytopenia. She was diagnosed with Ph-positive precursor B cell ALL. The patient's BCR-ABL fusion gene showed the e1a3 transcript. She received bone marrow transplantation (BMT) in the first complete remission (CR). However, the disease relapsed 4 months later, and she received a second BMT in the second CR, which caused lethal venoocculusive disease. The duration of the total clinical course was 18 months. We established a new cell line from the patient's leukemic cells at the time of relapse, which is very rare and useful for study as an atypical Ph-positive ALL model. The literature on Ph-positive leukemia lacking ABL exon 2 was also reviewed.

A Rare e14a3 (b3a3) BCR-ABL Fusion Transcript in Chronic Myeloid Leukemia

“…9 So far only five cases of CML with e1a3, 10 cases of e13a3, and five cases of e14a3 BCR-ABL transcripts have been reported. 10,11 These rare transcripts are also found in acute lymphocytic leukemia, with six cases reported previously. 11 These uncommon transcripts may be under-reported, since RT-PCR-based assays may fail to detect these fusions due to the location of the primers and probes used.…”

“…10,11 These rare transcripts are also found in acute lymphocytic leukemia, with six cases reported previously. 11 These uncommon transcripts may be under-reported, since RT-PCR-based assays may fail to detect these fusions due to the location of the primers and probes used. 12,13 In our clinical experience, we have processed specimens from approximately 450 individuals with CML in the last 4 years.…”

Acute Lymphoblastic Leukaemia with an e1a3 <i>BCR-ABL1</i> Fusion

“…Clues to any prognostic significance of the e1a3 BCR-ABL1 type in Ph+ ALL are confounded by the small numbers of patients reported and the variety of treatment regimes employed although there appears to be a similar poor outcome in those adult patients previously reported [2,5,7] to patients with the common BCR-ABL1 fusion transcripts and, with the present case, a slight female predominance (6/9) of this genotype.…”

“…The e1a3 BCR-ABL1 variant fusion transcript, lacking ABL1 exon a2 that partially encodes the src homology 3 (SH3) domain, has been described in three cases of chronic myeloid leukaemia (CML), all with a relatively indolent clinical course [3,4] . In Ph+ ALL, this BCR-ABL1 genotype has only been reported previously in 8 adult patients [2,[5][6][7] and 1 paediatric case [8] , making any relationships between phenotype and outcome difficult to ascertain. We describe the clinical course of a further case of Ph+ ALL with an e1a3 BCR-ABL1 fusion.…”

Complete cytogenetic response to Nilotinib in a chronic myeloid leukemia case with a rare e13a3(b2a3) BCR-ABL fusion transcript: A case report

“…By contrast, the SH3 domain is required for activation of signal transducer and activator of transcription 5 by the BCR-ABL protein, leading to full leukemogenesis. Thus, deletion of the SH3 domain may induce a less progressive clinical course (5,11). The BCR-ABL a3 breakpoint does not alter the sequence coding for the ATP/imatinib binding domain, but alterations in tertiary structure compared with a typical a2 fusion could affect drug response.…”