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Detection of Novel t(12;17)(p12;p13) in Relapsed Refractory Acute Myeloid Leukemia by Anchored Multiplex PCR(AMP)-based Next-Generation Sequencing

Badar, Talha, MD*; Johnson, Laura, PhD; Trifilo, Katelyn, BS; Wang, Helen, PhD; Kudlow, Brian A., PhD; Padron, Eric, MD; Pappenhausen, Peter R., PhD§; Hussaini, Mohammad O., MD

Applied Immunohistochemistry & Molecular Morphology: March 2019 - Volume 27 - Issue 3 - p e28–e31
doi: 10.1097/PAI.0000000000000477
Online Articles: Case Report

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)[20] 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:

Received November 1, 2016

Accepted November 1, 2016

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