RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM)

SCHLEGELBERGER, BRIGITTE; HELLER, PAULA G.

SEMINARS IN HEMATOLOGY

W B SAUNDERS CO-ELSEVIER INC

Año: 2017 vol. 54 p. 75 - 80

0037-1963

In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically present with 1) mild to moderate thrombocytopenia with normal-sized platelets; 2) functional platelets defects leading to prolonged bleeding; and 3) an increased risk to develop MDS, AML or T-ALL. Hematological neoplasms in carriers of a germline RUNX1 mutation need additional secondary mutations or chromosome aberrations to develop. If a disease-causing mutation is known in the family, it is important to prevent hematopoietic stem cell transplantation from a sibling or other relative carrying the familial mutation. First experiments introducing a wild-type copy of RUNX1 into iPSC lines from patients with FPDMM appear to demonstrate that by gene correction reversal of the phenotype may be possible.