High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML.

Autor:	Simon L; The Leucegene Project at Institute for Research in Immunology and Cancer and., Spinella JF; The Leucegene Project at Institute for Research in Immunology and Cancer and., Yao CY; The Leucegene Project at Institute for Research in Immunology and Cancer and., Lavallée VP; The Leucegene Project at Institute for Research in Immunology and Cancer and., Boivin I; The Leucegene Project at Institute for Research in Immunology and Cancer and., Boucher G; The Leucegene Project at Institute for Research in Immunology and Cancer and., Audemard E; The Leucegene Project at Institute for Research in Immunology and Cancer and., Bordeleau ME; The Leucegene Project at Institute for Research in Immunology and Cancer and., Lemieux S; The Leucegene Project at Institute for Research in Immunology and Cancer and.; Department of Biochemistry, Université de Montréal, Montréal, QC, Canada., Hébert J; The Leucegene Project at Institute for Research in Immunology and Cancer and.; Division of Hematology-Oncology and.; Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and.; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada., Sauvageau G; The Leucegene Project at Institute for Research in Immunology and Cancer and.; Division of Hematology-Oncology and.; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 May 21; Vol. 135 (21), pp. 1882-1886.
DOI:	10.1182/blood.2019003357
Abstrakt:	RUNX1 is mutated in ∼10% of adult acute myeloid leukemia (AML). Although most RUNX1 mutations in this disease are believed to be acquired, they can also be germline. Indeed, germline RUNX1 mutations result in the well-described autosomal-dominant familial platelet disorder with predisposition to hematologic malignancies (RUNX1-FPD, FPD/AML, FPDMM); ∼44% of affected individuals progress to AML or myelodysplastic syndromes. Using the Leucegene RUNX1 AML patient group, we sought to investigate the proportion of germline vs acquired RUNX1 mutations in this cohort. Our results showed that 30% of RUNX1 mutations in our AML cohort are germline. Molecular profiling revealed higher frequencies of NRAS mutations and other mutations known to activate various signaling pathways in these patients with RUNX1 germline-mutated AML. Moreover, 2 patients (mother and son) had co-occurrence of RUNX1 and CEBPA germline mutations, with variable AML disease onset at 59 and 27 years, respectively. Together, these data suggest a higher than anticipated frequency of germline RUNX1 mutations in the Leucegene cohort and further highlight the importance of testing for RUNX1 mutations in instances in which allogeneic stem cell transplantation using a related donor is envisioned. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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