Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation

Biomarker Research
Isaac Ks NgLip Kun Tan

Abstract

Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell tran...Continue Reading

References

Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E OgawaY Ito
Apr 2, 1999·European Journal of Biochemistry·M Wolf-WatzT Härd
Aug 15, 2002·Blood·D Gary Gilliland, James D Griffin
May 15, 2008·European Journal of Human Genetics : EJHG·Mylène Béri-DexheimerPhilippe Jonveaux
Jul 2, 2008·Haematologica·Konstanze Döhner, Hartmut Döhner
Aug 9, 2008·The Journal of Biological Chemistry·Yusuke SatohYuzuru Kanakura
Sep 16, 2011·Journal of Hematology & Oncology·Shinichiro Takahashi
Nov 19, 2011·Blood·Hervé Dombret
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Kentson Lam, Dong-Er Zhang
Jun 16, 2012·Blood·Christian Thiede
Jul 25, 2012·BMC Cancer·Anne MuratiDaniel Birnbaum
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·M Ryan Corces-ZimmermanRavindra Majeti
Aug 28, 2014·Nature Communications·Akihide YoshimiMineo Kurokawa
Nov 6, 2014·British Journal of Haematology·Gro G PløenAnni Aggerholm
Aug 26, 2015·JAMA : the Journal of the American Medical Association·Jeffery M KlcoTimothy J Ley
Feb 21, 2016·Journal of Clinical Pathology·Benedict YanWee-Joo Chng
Mar 25, 2016·Journal of Clinical Pathology·Benedict YanLiang Piu Koh
Dec 3, 2016·Leukemia·H P Koeffler, G Leong

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Citations

Aug 8, 2018·International Journal of Hematology·Kateřina Staňo KozubíkMichael Doubek
Nov 4, 2020·American Journal of Medical Genetics. Part a·Floor A M PostemaRaoul C Hennekam
Jun 7, 2021·Biomarker Research·Shichao WangShaobing Gao
Aug 13, 2021·Frontiers in Oncology·Jason H Kurzer, Olga K Weinberg

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Methods Mentioned

BETA
Flow Cytometry
MDS

Software Mentioned

Illumina VariantStudio
TruSeq Amplicon

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