A Rare, In-Frame <i>BCR-ABL</i> Fusion (e13a3) in a Patient with an Aggressive Chronic Myeloid Leukaemia

Abstract

We have identified a rare BCR-ABL chimaeric gene with multiplex and nested RT-PCR in a patient with an unusually aggressive chronic myeloid leukaemia. cDNA sequencing showed an in-frame rearrangement with a breakpoint in BCR exon e13 (b2) and fusion with ABL exon 3 following skipping of the entire ABL exon a2. These data confirm the heterogeneity of breakpoints in BCR-ABL rearrangements.

An analysis of multiplex-PCR in the detection of BCR-ABL transcripts in hematological disorders

“…The directly sequenced PCR product revealed a b3a3 junction and absence of ABL exon 2-derived sequences. The frequency of such variant rearrangements is very low in both CML and ALL, and few cases have been reported in the literature (Iwata et al, 1994;Otazu et al, 2002;Liu et al, 2003;Paz-Y-Mino et al, 2003). These observations confirm the great genetic heterogeneity produced when a bcr-abl rearrangement occurs.…”

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

“…In nearly all patients with the BCR-ABL gene, the BCR-a2 junction is detected, such as b2a2 and/or b3a2, e1a2, and e19a2, which are transcribed into major, minor, and micro bcr-abl messenger RNA, respectively. A BCR-ABL gene lacking ABL a2 has; however, been recognized by several groups (Table 1) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

“…The outcomes in CML cases in blastic crisis were also poor [8,9]. In some CML cases, especially in recent, newly diagnosed CML cases, the chronic phase has been continuing for a long time mainly with imatinib mesylate [17][18][19][20][21][22]. This prognostic difference between ALL and CML might be due to the essential variation in leukemic cells themselves in terms of aggressiveness.…”

An e13a3 BCR‐ABL1 fusion transcript in variant t(9;22;17)(q34;q11;q21)‐positive adult acute lymphoblastic leukemia

“…Most BCR-ABL1 fusion transcripts are e13a2 (b2a2) or e14a2 (b3a2); some variant patients have been reported expressing the less commonly, e1a2 or e19a2. In addition, very rare atypical transcript types, such as e1a3, e14a3, or e6a2, have been described [2][3][4][5][6][7][8][9][10].…”

“…The mechanisms of the generation of the different BCR-ABL1 fusion transcripts are also not known. Otazu et al [8] noted that the last codon of BCR e13 (AAG, coding for lysine) is the same as the last codon of ABL1 a2, which is normally spliced to ABL1 a3. They speculated that the deletion of ABL1 a2 might arise from a misrecognition of splicing sites.…”