John Libbey Eurotext



Germline RUNX1 mutations/deletions and genetic predisposition to haematological malignancies Ahead of print


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1 Inserm, UMR1287, Villejuif, France; Gustave Roussy, Villejuif, France; Université Paris XI, UMR1287, Gustave Roussy, Villejuif, France
2 Laboratoire d’hématologie, biologie moléculaire des hémopathies, CHU de Lille; University of Lille, Inserm UMR-S 1277, équipe Facteurs de persistance des cellules leucémiques
* Correspondence

The RUNX1 gene encodes for the alpha subunit of the core binding factor, a heterodimeric transcription factor complex involved in haematopoietic differentiation. RUNX1 germline mutations and deletions are implicated in familial platelet disorder with predisposition to acute myeloid leukaemia (FPD/AML). They have been described in more than 200 families and it is estimated that more than 6,000 families worldwide are affected by this genetic predisposition. The classic phenotype of individuals carrying this constitutional abnormality includes mild to moderate thrombocytopaenia with normal volume, abnormal platelet functions (associated with or without a tendency to bleed),1 dysmegakaryopoiesis, and a predisposition to develop haematological malignancies of various phenotypes (acute myeloid leukaemia, myelodysplastic syndromes, acute T-cell lymphoblastic leukaemia) at any age. When the phenotype is suggestive, but sequencing remains negative, the diagnostic algorithm should include a copy number analysis to look for large deletions. Haematopoietic stem cell transplantation is the only curative therapy but involves taking precautions when selecting intrafamilial donors. Monitoring individuals who have not yet developed a haematological malignancy has not yet been codified but regular follow-up with complete blood count is recommended, coupled with screening for additional molecular abnormalities predicting a malignant transformation.