Inserm, UMR1287, Villejuif, France ; Gustave Roussy, Villejuif, France; Université Paris XI, UMR1287, Gustave Roussy, Villejuif, France
Laboratoire d’hématologie, biologie moléculaire des hémopathies, CHU de Lille ; université de Lille, Inserm UMR-S 1277, équipe Facteurs de persistance des cellules leucémiques
The RUNX1 gene encodes for the alpha subunit of the core binding factor, a heterodimeric transcription factor complex involved in hematopoietic differentiation. RUNX1 germline mutations and deletions are implicated in the FPD/AML (familial platelet disorder with predisposition to acute myeloid leukemia). 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 classical phenotype of individuals carrying this constitutional abnormality includes mild to moderate thrombocytopenia with normal volume, abnormal platelet functions (associated with a bleeding tendency or not), dysmegakaryopoiesis and predisposition to the development of hematological malignancies of various phenotypes (acute myeloid leukemia, myelodysplastic syndromes, acute T-cell lymphoblastic leukemia) 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. Hematopoietic stem cell transplantation is the only curative therapy but implies precautions for the selection of intrafamilial donors. Monitoring of individuals who have not yet developed a hematological malignancy is not yet codified but it is recommended to provide a regular follow-up with complete blood count, associated with the screening of additional molecular abnormalities predicting a malignant transformation.