Letter to the EditorSustained clinical remission despite suboptimal molecular response to imatinib in e1a2 BCR–ABL chronic myeloid leukemia
Introduction
Approximately 90–95% of chronic myeloid leukemia (CML) patients have evidence of a Philadelphia (Ph) chromosome with nearly all expressing either one or both e13a2 or e14a2 BCR–ABL fusion transcripts [1]. A number of 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. Rarely, e1a2 BCR–ABL transcripts, usually associated with Ph-positive acute lymphoblastic leukemia, are found to be the sole BCR–ABL species in CML. Although the introduction of imatinib therapy has been a major advance in the treatment of CML [2], response to imatinib in e1a2 BCR–ABL CML has until recently been anecdotal [3], [4]. Two recent reports identifying patients with e1a2 BCR–ABL CML have highlighted the relatively poor response to frontline imatinib and subsequent tyrosine kinase inhibitor (TKI) therapy in this genotype [5], [6]. Complete cytogenetic and molecular responses are infrequent and when obtained, are often short-lived, suggesting close molecular monitoring throughout treatment with allogeneic stem cell transplantation, if eligible, to be considered early in this disease. Mutations in the ABL kinase domain may not completely explain the poor outcome with resistance possibly mediated by BCR-ABL independent mechanisms [6]. A patient with e1a2 BCR–ABL CML is described who achieved a hematological remission, a delayed complete cytogenetic remission (CCyR) and who maintains only a suboptimal molecular response to imatinib therapy though remaining clinically stable for longer than 2 years after initial presentation.
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Case report
A 61-year-old female presented with an incidental finding of a raised white blood cell count. She suffered from a non-q wave myocardial infarction 7 years previously and was otherwise well. Peripheral full blood count showed WCC 35.4 × 109/L with a monocytosis of 3.89 × 109/L, hemoglobin of 17.4 g/L, platelets 627 × 109/L and a basophilia of 0.35 × 109/L. Atypical monocyte morphology was noted with no peripheral blasts and there was no palpable spleen. The patient had a low risk Sokal score of 0.78. The
Discussion
Variant BCR–ABL fusion genes afford the opportunity to explore genotype–phenotype relationships in CML with the monocytosis and atypical monocyte morphology observed at diagnosis in this patient characteristic of e1a2 BCR–ABL CML [8]. However, it remains unclear whether relatively small numbers of patients with these variant transcripts have similar responses and prognoses to e13a2/e14a2 BCR–ABL CML. Although infrequent case reports have described a relatively indolent clinical course even
Conflict of interest
The authors report no conflicts of interest.
Acknowledgements
None.
Contributions. S.E.L. conceived the study and wrote the letter. M.C. and K.H. performed RQ-PCR analysis. J.K. performed cytogenetic analysis. M.R.C. provided patient care and clinical information.
References (11)
- et al.
Molecular biology of bcr-abl1 positive chronic myeloid leukemia
Blood
(2009) - et al.
Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes and prognostic significance
Blood
(2009) - et al.
Chronic myeloid leukemia with p190 BCR-ABL: prevalence, morphology, tyrosine kinase inhibitor response, and kinase domain mutation analysis
Blood
(2009) - et al.
Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet
Blood
(2006) - et al.
Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results
Blood
(2006)