RUNX1-familial platelet disorder (RUNX1-FPD) with predisposition to hematologic malignancies is a hereditary disorder due to a mutation in the gene RUNX1 ¹. The mutation is passed down from generation to generation.
The link between germline RUNX1 mutations and blood cancer was first discovered in 1999.² Since then studies have estimated that the average lifetime risk of getting a blood cancer with mutations in the RUNX1 gene is close to 50%. It is important to note that there is a huge range in incidence of cancer between families, with some being as low as 11% and others as high as 100%.¹ The predominant type of blood cancer RUNX1-FPD patients acquire is acute myeloid leukemia (AML), the second deadliest of all blood cancers.⁴ Other types of hematologic malignancies may also occur in patients, including myelodysplastic syndromes, T-cell acute lymphoblastic leukemia, and non-Hodgkin lymphoma.¹ Thirty-three years is the average age of onset of a blood cancer for a person carrying a germline RUNX1 mutation, while the average age of onset in the general population is 68 years of age. Moreover, 50% of families with RUNX1-FPD have at least one or more children who progress to cancer. ³ ⁵ ⁶
Godley, LA. Inherited predisposition to acute myeloid leukemia. Seminars in Hematology. 2014;51(4):306-321.
Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23(2):166-175.
Brown AL, Churpek JE, Malcovati L, et al. Recognition of familial myeloid neoplasia. Seminars in Hematol. 2017;54:60-68.
Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Mortality - All COD, Aggregated with State, Total U.S. (1969-2015), National Cancer Institute, DCCPS, Surveillance Research Program, released December 2017. Underlying mortality data provided by NCHS (www.cdc.gov/nchs).
Owen CJ. Toze CL, Koochin A, et al. Five new pedigrees with inherited RUNX1mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood. 2008;112(12):4636-45.
Bannon SA, DiNardo CD. Hereditary predispositions to myelodysplastic syndrome. Int J Mol Sci. 2016;17(6).