Letter to the EditorNilotinib and allogeneic stem cell transplantation in a chronic myeloid leukemia patient with e6a2 and e1a2 BCR-ABL transcripts
Introduction
Nearly all chronic myeloid leukemia (CML) patients express either one or both e13a2 or e14a2 BCR-ABL fusion transcripts. Variant transcripts arising from outside the usual breakpoint regions of both BCR and ABL genes have been described in CML that involve either fusion of alternate exons, insertions or breakpoints within exons. One of the most frequently reported of these variant transcripts is that in which BCR exon 6 is fused to ABL exon a2 resulting in a transcriptionally active e6a2 fusion [1], described in CML [2] and more rarely in Ph-positive acute myeloid leukemia (AML) and other hematological malignancies [3], [4]. As few e6a2 BCR-ABL CML patients have been reported, the phenotype of this particular genotype remains unclear although it has been hypothesized that the shorter e6a2 BCR-ABL transcripts promote a more aggressive clinical phenotype and early transformation due to lack of regulatory BCR domains necessary for proliferation and signal transduction interactions [5]. The efficacy of tyrosine kinase inhibitors (TKI) in CML patients with e6a2 BCR-ABL fusion transcripts is unclear with conflicting reports in the literature. Here we report an imatinib unresponsive CML patient in accelerated phase co-expressing e6a2 and e1a2 BCR-ABL transcripts who achieved a major molecular response to a second generation TKI followed by potentially curative therapy of allogeneic stem cell transplantation (ASCT).
Section snippets
Case report
A 36-year old male presented with fatigue had a peripheral full blood count showing leukocytosis (WCC 39.5 × 109/L) with basophilia (1.8 × 109/L), anaemia (hemoglobin 11.8 g/dL) and platelet count 341 × 109/L. On examination the spleen was palpable 15.5 cm below the costal margin with no hepatomegaly. Blood film examination showed nucleated red blood cells, immature myeloid precursors and circulating myeloblasts. A hypercellular bone marrow aspirate was consistent with a myeloproliferative disorder
Discussion
The described patient presented in chronic phase with co-expression of e6a2 and e1a2 BCR-ABL transcripts, a phenomenon previously described in only one CML patient bearing different der(9) deletions in separate clones [7], with the e1a2 transcripts probably representing low level alternative exon splicing in this instance. Effective use of nilotinib is previously unreported in e6a2 BCR-ABL CML; however, case reports have demonstrated the value of the second generation TKI, dasatinib, in
Conflict of interest
The authors report no conflicts of interest.
Acknowledgements
Contributions. S.E.L. conceived the study and wrote the letter. M.C. performed RQ-PCR analysis. J.K. performed cytogenetic analysis. K.F., G.C. and E.C. provided patient care and clinical information.
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AML with BCR-ABL1 Fusion treated with Imatinib, a Hypomethylating Agent and Venetoclax
2022, Leukemia Research ReportsCitation Excerpt :Elderly patients with co-morbidities are typically not eligible to standard intensive chemotherapy nor to allogeneic hematopoietic cellular transplantation (allo-HCT). On the other hand, TKIs are effectively used as salvage and bridging therapy to allo-HCT, as well as maintenance therapy post allo-HCT, improving outcomes in Ph+ AML [8]. The combination of venetoclax and a hypomethylating agent (HMA) has emerged as a new standard for elderly and/or unfit patients diagnosed with AML in view of improved response rates and comparable toxicity when compared to HMA alone [9].