Rare BCR-ABL fusions highlighted in CML

By Lynda Williams, Senior medwireNews Reporter

Chronic myeloid leukaemia (CML) patients with rare BCR-ABL fusions may be missed by quantitative polymerase chain reaction (Q-PCR), research suggests.

Jinlan Pan, from The First Affiliated Hospital of Soochow University in Suzhou, China, and co-authors reviewed medical records for 2381 CML patients who tested positive for the Philadelphia chromosome.

They identified five (0.21%) cases where the patients did not test positive at Q-PCR for the most common fusion transcripts, e13a2, e14a2 or e1a2; DNA sequencing revealed a fusion between BCR exon 14 and ABL exon 3 (e14a3).

“To ensure the detection and clarify the natural incidence of the rare BCR-ABL variants and reduce the risk of being missed, different approaches including cytogenetics, [fluorescent in situ hybridisation] and Q-PCR should be used in combination, especially if negative results have been obtained by Q-PCR for newly-diagnosed CML”, the researchers emphasise.

“Of course, if a rare BCR-ABL has been found, the appropriate primers should be designed for Q-PCR to monitor the BCR-ABL minimal residual disease.”

The researchers report in Leukemia & Lymphoma that four of the e14a3 patients were in chronic phase at time of diagnosis and one patient was in accelerated phase.

One patient achieved a partial response to initial treatment with hydroxycarbamide and alpha-interferon, but the other four did not respond to hydroxycarbamide alone or in combination.

Three patients achieved complete cytogenetic remission (CCyR) with imatinib therapy, two of whom were alive at time of reporting, after 66 and 101 months. The third patient progressed to lymphoid blast crisis after 14 months, showed additional abnormalities in karyotype analysis, and died despite vincristine and prednisone therapy.

The fourth patient achieved CCyR after switching from imatinib to dasatinib therapy and was alive at the time of reporting, after 112 months. The fifth patient achieved CCyR following allogeneic haematopoietic stem cell transplantation and BCR-ABL remained undetectable at time of reporting after 30 months.

Pan et al therefore suggest that future patients with the rare e14a3 fusion should be considered for tyrosine kinase inhibitor therapy or transplantation.

“More cases should be accumulated to elucidate the clinical and prognostic features of CML cases with e14a3”, they conclude.

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