Identification of a rare e8a2 BCR-ABL fusion gene in three novel chronic myeloid leukemia patients treated with imatinib

Cayuela, Jean‐Michel; Rousselot, Philippe; Nicolini, Frank; Espinouse, Daniel; Ollagnier, Christophe; Bui-Thi, M H; Chabane, Kaddour; Raffoux, Emmanuel; Callet‐Bauchu, Evelyne; Tigaud, Isabelle; Magaud, Jean‐Pierre; Hayette, Sandrine

doi:10.1038/sj.leu.2403986

Cited by 14 publications

(16 citation statements)

References 8 publications

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“…Furthermore, some patients have atypical breakpoints, which are different from the above junctions. CML patients with different types of e8a2 BCR-ABL transcript have been reported [2,3,4,5,6]. In the current study, we identified a CML patient in the late chronic phase (CP) who possessed a novel e8a2 BCR-ABL transcript variant and her responses were followed during 65-month imatinib treatment.…”

Section: Introductionmentioning

confidence: 87%

“…In light of the fact that the direct junction between BCR exon 8 and ABL exon 2 results in the generation of a premature stop codon, an insertion of sequences or/and breakpoint within the BCR exon 8 is needed to produce an in-frame e8a2 transcript. Most reported inserted sequences were inverted partial ABL intron 1b [2,3,4,5,6]. Demrhi et al [2] reported 1 case with a 151-bp insertion from intron Ia.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent reports demonstrate that such patients usually had good responses to imatinib. Cayuela et al [3] reported that 3 patients with e8a2 BCR-ABL transcript achieved complete cytogenetic remission and a major molecular response(MMoR) at a median of 7 and 20 months of imatinib treatment, respectively. Tchirkov et al [4] also reported on 1 patient with e8a2 BCR-ABL transcript who achieved a MMoR within the first year of imatinib treatment.…”

Section: Discussionmentioning

confidence: 99%

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Imatinib Mesylate Resistance in a Chronic Myeloid Leukemia Patient with a Novel e8a2 BCR-ABL Transcript Variant

Qin

Jiang²,

Jiao³

et al. 2008

Acta Haematol

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Background: The vast majority of chronic myeloid leukemia (CML) patients express the BCR-ABL transcript with the b2a2 (e13a2) and/or b3a2 (e14a2) junctions. However, some rare cases have atypical breakpoints. Methods and Results: We identified a CML patient with a unique e8a2 BCR-ABL transcript variant. It contained the first 114 nucleotides of BCR exon 8, with an insertion of 16 nucleotides from the 3′ end of ABL intron 1a, followed by ABL exon 2. Due to her uncontrolled thrombocytosis after 3 years of interferon-α treatment, the patient received imatinib at a dosage of 400 mg/day. Though achieving a sustained and complete hematological response after 3 months, she was resistant to imatinib during the entire 65-month imatinib treatment. That is, she failed to achieve major cytogenetic response and there was no significant decrease in her BCR-ABL transcript levels. Meanwhile, an M351T mutant was detected at 18 months after the start of imatinib treatment. Conclusion: ABL point mutation is also a mechanism of imatinib resistance for CML patients with the BCR-ABL transcript variant.

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Section: Introductionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Imatinib Mesylate Resistance in a Chronic Myeloid Leukemia Patient with a Novel e8a2 BCR-ABL Transcript Variant

Qin

Jiang²,

Jiao³

et al. 2008

Acta Haematol

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“…A larger PCR analysis using a forward primer in the BCR gene (ENF402 6 ) and a reverse primer (5'GCCCTCGTACAC-CTCCCCGTA3') in the ABL exon a4 revealed an atypical e8a4 after direct sequencing ( Figure 1B). However, unlike the e8a2 transcripts previously described, [8][9][10] the direct junction between BCR exon e8 and ABL exon a4 led to the preservation of the ORF encompassing the whole oncogenic domains of the ABL tyrosine kinase. The quantification of the e8a4 was carried out using RQ-PCR with an e8 forward primer from BCR gene, 10 the same reverse primer and a new probe (FAM 5'TCTACGTCTC-CTCCGAGAGC3'TAMRA) in ABL exon a4.…”

Section: Identification Of a Novel E8/a4 Bcr/abl Fusion Transcript Inmentioning

confidence: 69%

“…However, unlike the e8a2 transcripts previously described, [8][9][10] the direct junction between BCR exon e8 and ABL exon a4 led to the preservation of the ORF encompassing the whole oncogenic domains of the ABL tyrosine kinase. The quantification of the e8a4 was carried out using RQ-PCR with an e8 forward primer from BCR gene, 10 the same reverse primer and a new probe (FAM 5'TCTACGTCTC-CTCCGAGAGC3'TAMRA) in ABL exon a4. With a serial 10-fold dilution series for e8a4 cDNA from the patient's sample, the assay was found to be linear over at The number of e8a4 copies in the non diluted sample was estimated to be 13,600 for 10,000 copies of ABL which agreed with data obtained by cytogenetic analysis and confirmed that the e8a4 must be the oncogenic fusion transcript.…”

Section: Identification Of a Novel E8/a4 Bcr/abl Fusion Transcript Inmentioning

confidence: 69%

Identification of a novel e8/a4 BCR/ABL fusion transcript in a case of a transformed Sezary syndrome

Callet‐Bauchu¹,

Salles²,

Gazzo³

et al. 2007

Haematologica

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Molecular characterization and follow‐up of five CML patients with new BCR–ABL1 fusion transcripts

Huet

Dulucq

Chauveau

et al. 2015

Genes Chromosomes & Cancer

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We report five chronic myeloid leukaemia (CML) patients in whom we identified and characterized undescribed BCR-ABL1 fusion transcripts. We investigated the precise features of the molecular rearrangements and the minimal residual disease follow-up for these five patients. Three resulted from new rearrangements between the BCR and ABL1 sequences (the breakpoints being located within BCR exon 13 in two cases and within BCR exon 18 in one case). The other two cases revealed a complex e8-[ins]-a2 fusion transcript involving a third partner gene, PRDM12 and SPECC1L, respectively. Moreover, single nucleotide polymorphism-array analysis performed in the latter two cases showed copy number alterations shared by the two patients, thus identifying genes that were deleted during rearrangement and suggesting their potential role in CML pathogenesis. Interestingly, we highlight that the prognosis of alterations, such as the presence of an e8a2 transcript or the deletion of various genes, which have been controversial, may be definitively erased by the introduction of tyrosine kinase inhibitors (TKIs).

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Identification of a rare e8a2 BCR-ABL fusion gene in three novel chronic myeloid leukemia patients treated with imatinib

Cited by 14 publications

References 8 publications

Imatinib Mesylate Resistance in a Chronic Myeloid Leukemia Patient with a Novel e8a2 BCR-ABL Transcript Variant

Imatinib Mesylate Resistance in a Chronic Myeloid Leukemia Patient with a Novel e8a2 BCR-ABL Transcript Variant

Identification of a novel e8/a4 BCR/ABL fusion transcript in a case of a transformed Sezary syndrome

Molecular characterization and follow‐up of five CML patients with new BCR–ABL1 fusion transcripts

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