Broad genomic workup including optical genome mapping uncovers a DDX3X : MLLT10 gene fusion in acute myeloid leukemia.

Autor:	Nilius-Eliliwi V; Department of Medicine, Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Tembrink M; Human Genetics, Ruhr-University Bochum, Bochum, Germany., Gerding WM; Human Genetics, Ruhr-University Bochum, Bochum, Germany., Lubieniecki KP; Human Genetics, Ruhr-University Bochum, Bochum, Germany., Lubieniecka JM; Human Genetics, Ruhr-University Bochum, Bochum, Germany., Kankel S; Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany., Liehr T; Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany., Mika T; Department of Medicine, Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Dimopoulos F; Department of Medicine, Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Döhner K; Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany., Schroers R; Department of Medicine, Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Nguyen HHP; Human Genetics, Ruhr-University Bochum, Bochum, Germany., Vangala DB; Department of Medicine, Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Sep 09; Vol. 12, pp. 959243. Date of Electronic Publication: 2022 Sep 09 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.959243
Abstrakt:	In acute myeloid leukemia (AML), treatment decisions are currently made according to the risk classification of the European LeukemiaNet (ELN), which is based on genetic alterations. Recently, optical genome mapping (OGM) as a novel method proved to yield a genome-wide and detailed cytogenetic characterization at the time of diagnosis. A young female patient suffered from a rather unexpected aggressive disease course under FLT3 targeted therapy in combination with induction chemotherapy. By applying a "next-generation diagnostic workup" strategy with OGM and whole-exome sequencing (WES), a DDX3X: MLLT10 gene fusion could be detected, otherwise missed by routine diagnostics. Furthermore, several aspects of lineage ambiguity not shown by standard diagnostics were unraveled such as deletions of SUZ12 and ARPP21 , as well as T-cell receptor recombination. In summary, the detection of this particular gene fusion DDX3X: MLLT10 in a female AML patient and the findings of lineage ambiguity are potential explanations for the aggressive course of disease. Our study demonstrates that OGM can yield novel clinically significant results, including additional information helpful in disease monitoring and disease biology. Competing Interests: DV received speaker’s honoraria from Roche, consultant’s honoraria from Pfizer, Bristol Myers Squibb and Gilead as well as travel support and congress registration fees from Gilead and Celgene. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Nilius-Eliliwi, Tembrink, Gerding, Lubieniecki, Lubieniecka, Kankel, Liehr, Mika, Dimopoulos, Döhner, Schroers, Nguyen and Vangala.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu