Although several technologies can be used to detect gene fusions, anchored multiplex PCR next-generation sequencing (AMP-NGS) offers the advantage of novel fusion detection and the ability to multiplex multitudinous genes. We applied AMP-NGS technology in the evaluation of a 56-year-old gentleman with myelodysplastic syndrome transformed acute myeloid leukemia (AML). Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy. At progression patients had normal cytogenetics but NGS profiling showed ETV6 c.416_417del CT frame shift and U2AF1 S34F mutations. Patient attains brief remission of 2 months after induction chemotherapy and then he was refractory to 2 salvage chemotherapy regimens. Reassessment after failing second salvage, identified t(12;17)(p13;p13) by karyotype. It was postulated that the 12p13 locus might represent a new rearrangement of ETV6. AMP-NGS confirmed involvement of the ETV6 with discovery of a novel fusion partner, HIC1. The detection of the novel fusion partners was supported by the breakpoints originally observed by karyotype. This discovery of ETV6-HIC1 gene fusion by AMP-NGS technology provided new insight into a leukemogenic pathway in AML. Future use of this technology can serve as an adjunct tool in workup of patients with AML and can also help in formulating therapeutic strategies.
*Department of Internal Medicine, Brandon Regional Hospital, Brandon
‡Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, FL
†ArcherDx, Boulder, CO
§Labcorp, Durham, NC
T.B., M.O.H., and L.J.: conception and designed research. T.B. and M.O.H.: performed research. M.O.H. and E.P.: acquisition of data (acquired and managed patients). T.B. and M.O.H.: analyzed data. M.O.H., K.T., H.W., B.K., and P.R.P.: performed experiments. T.B. and M.O.H.: writing, review, and/or revision of the manuscript.
The authors declare no conflict of interest.
Reprints: Mohammad O. Hussaini, MD, Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612 (e-mail: firstname.lastname@example.org).
Received November 1, 2016
Accepted November 1, 2016