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

Liu, Bei; Zhang, Wei; Ma, Haizhen

doi:10.3892/mmr.2016.4826

Cited by 13 publications

(9 citation statements)

References 10 publications

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“…In the present report we describe the clinical history of a very elderly CML patient with the t(9;22) reciprocal translocation detected by G-banding encoding for a rare e13a3 BCR-ABL1 transcript. Although individual accounts of single patients exhibiting BCR-ABL1 transcripts lacking exon 2 of ABL1 have been previously published (21)(22)(23), to the best of our knowledge this is the first case reporting the occurrence of this unusual fusion in a very elderly individual treated with a second-generation TKI. Uncommon BCR-ABL1 isoforms can go undetected since the classical RT-PCR multiplex employed to diagnose the disease can sometimes generate atypical PCR fragments often interpreted as nonspecific products.…”

Section: Discussionmentioning

confidence: 87%

Efficacy of Dasatinib in a Very Elderly CML Patient Expressing a Rare E13a3 Bcr-Abl1 Fusion Transcript: A Case Report

et al. 2019

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We report the case of an 89-year-old male diagnosed with chronic-phase CML and expressing a rare e13a3 BCR-ABL1 fusion transcript. His cytogenetic analysis showed the t(9;22) translocation generating the Philadelphia chromosome (Ph), with a multiplex RT-PCR detecting an atypical fragment. Using two primers complementary to exon 10 of BCR and exon 4 of ABL1, a larger PCR product was observed, where after Sanger sequencing, an e13a3 BCR-ABL1 transcript was revealed. Given the diagnosis, the patient received 100 mg of dasatinib every other day and was then monitored by measuring both hematological and cytogenetic parameters, while his BCR-ABL1 transcripts were examined by PCR and semi-nested-PCR. According to the 2013 European Leukemia Network criteria, after six months of dasatinib the patient's response was classified as warning as he displayed 20% of Philadelphia-positive metaphases. Sequencing of the ABL1 catalytic domain did not detect point mutations. A complete cytogenetic response was achieved after one year of dasatinib. However, semi-nested-PCR confirmed the presence of the e13a3 BCR-ABL1 fusion transcript that has persisted up to the latest follow-up visit.The Philadelphia Chromosome (Ph) is generated by a reciprocal translocation t(9;22) (1, 2) leading to the assembly of a chimeric BCR-ABL1 oncogene that modulates the proliferation, apoptotic rate, cytoskeletal dynamics and microenvironment interaction of the hematopoietic stem cell, thereby giving rise to chronic myeloid leukemia (CML) (3-7). Usually, the BCR-ABL1 fusion encompasses exon 2 of the ABL1 gene that is fused in frame with one of three different breakpoints on the BCR gene: i) major (M-BCR), ii) minor (m-BCR) and iii) micro (μ-BCR). M-BCR includes the fusion transcripts in proximity of exons 13 or 14 of BCR, generating the more common e13a2 or e14a2 BCR-ABL1 variants. The remaining m-BCR and μ-BCR breakpoint clusters involve less common rearrangements affecting exons 1 or 19 of BCR that generate the e1a2 (8) or e19a2 fusions, respectively (9). Moreover, additional uncommon breakpoints have been previously described involving BCR exons 6 and 8 or ABL1 exon 3 (10). Interestingly, BCR-ABL1 isoforms involving exon 3 of ABL1 (e13a3, e14a3 and e19a3) have been described both in CML patients (11-13), with contrasting clinical outcomes, and in individuals diagnosed with Ph+ acute lymphoblastic leukemia ( 14). In the present study we report the case of a very elderly CML patient expressing a rare e13a3 BCR-ABL1 transcript displaying a partially satisfactory response to dasatinib (DAS) treatment.

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Section: Discussionmentioning

confidence: 87%

Efficacy of Dasatinib in a Very Elderly CML Patient Expressing a Rare E13a3 Bcr-Abl1 Fusion Transcript: A Case Report

et al. 2019

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“…In fact, the use of conventional multiplex RT-PCR usually fails to detect uncommon BCR::ABL1 rearrangements due to the generation of atypical PCR products, which are often interpreted as nonspecific and may lead to misdiagnosis, thus excluding the patient from targeted therapy. While atypical transcripts in CML patients are increasingly reported (11)(12)(13)(14), the outcome seems to be adverse in some of the more "frequent rare" mutations such as e1a2 (15,16).…”

Section: Discussionmentioning

confidence: 99%

Atypical presentation of patients with chronic myeloid leukemia in chronic phase—Case report

et al. 2022

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The presence of the translocation t(9;22)(q34;q11), leading to the BCR::ABL1 fusion transcript, is the hallmark of chronic myeloid leukemia (CML). Nevertheless, atypical presentation at diagnosis can be challenging. However, although most patients with CML are diagnosed with the e13a2 or e14a2 BCR::ABL1 fusion transcripts, about 5% of them carry rare BCR::ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3, and e6a2. In particular, the e6a2 fusion transcript has been associated with clinically aggressive disease frequently presenting in accelerated or blast crisis phases. To date, there is limited evidence on the efficacy of front-line second-generation tyrosine kinase inhibitors for this genotype. Here, we report two patients, in whom the diagnosis of CML was challenging. The use of primers recognizing more distant exons from the common BCR::ABL1 breakpoint region correctly identified the atypical BCR::ABL1 e6a2 fusion transcript. Treatment with the second-generation tyrosine kinase inhibitor nilotinib was effective in our patient expressing the atypical e6a2 BCR::ABL1 fusion transcript.

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“…Moreover, the outcome of TKI therapy in patients with uncommon BCR-ABL1 transcripts has not yet been defined. As previous reports suggested excellent efficacy of NIL in patients harboring atypical BCR-ABL1 isoforms (30,32), we wanted to employ this compound for the patient described in this manuscript. Indeed, we observed a rapid decline in the overall number of leukemic cells and Ph-positive metaphases, and the patient achieved a CHR, CCyR and MR 3 within 6 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

Detection and Clinical Implications of a Novel BCR-ABL1 E12A2 Insertion/Deletion in a CML Patient Expressing the E13A2 Isoform

et al. 2019

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Background/Aim: The Philadelphia chromosome is the most frequent cytogenetic abnormality in chronic myelogenous (CML). More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement. Furthermore, about 5% of CML patients are diagnosed with rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. However, there is limited evidence concerning the clinical and prognostic implications of these infrequent oncogenic variants for CML patients receiving tyrosine kinase inhibitors (TKIs). Case Report: We describe a novel atypical e12a2 insertion/deletion (Ins/Del) BCR-ABL1 fusion identified in a CML 59-year-old man diagnosed with a common e13a2 BCR-ABL1 isoform. The use of primers recognizing more distant exons from the common BCR-ABL1 breakpoint region correctly identified and monitored in time the atypical e12a2 Ins/Del BCR-ABL1 fusion. Conclusion: Treatment with second-(nilotinib) and third-generation (ponatinib) TKIs was effective in suppressing leukemic clones exhibiting the atypical e12a2 Ins/Del BCR-ABL1.

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

Cited by 13 publications

References 10 publications

Efficacy of Dasatinib in a Very Elderly CML Patient Expressing a Rare E13a3 Bcr-Abl1 Fusion Transcript: A Case Report

Efficacy of Dasatinib in a Very Elderly CML Patient Expressing a Rare E13a3 Bcr-Abl1 Fusion Transcript: A Case Report

Atypical presentation of patients with chronic myeloid leukemia in chronic phase—Case report

Detection and Clinical Implications of a Novel BCR-ABL1 E12A2 Insertion/Deletion in a CML Patient Expressing the E13A2 Isoform

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