First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukaemia: correlation with the clinical phenotype.

GLEMBOTSKY ANA C.; MARIN OYARZUN CP.; DE LUCA G.; MARZAC C.; GOETTE NP.; AUGER N.; MARTA, RF.; RASLOVA H.; HELLER PG.

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Lugar: Pavia, Italia; Año: 2020

0390-6078

Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML) isan autosomal dominant condition characterized by abnormal platelet number and function and30-60% risk of haematologic malignancies, including myelodysplastic syndrome, acutemyelogenous leukaemia and T-cell lymphoblastic leukaemia.1 It is caused by heterozygousgermline mutations in the gene encoding the transcription factor RUNX1, which is essential inthe emergence of definitive haematopoiesis and plays a key role in the lymphoid andmegakaryocyte lineages.1,2 RUNX1 mutations predispose to leukaemia by inducing genomicinstability which favours the acquisition of secondary somatic mutations.3 Thrombocytopenia ismild to moderate with normal-sized platelets and most patients display a platelet function defectwith impaired platelet aggregation and dense-granule deficiency.1 However, the plateletphenotype is heterogeneous4 and even normal platelet count and function have been reported inrare carriers of RUNX1 mutations,5 highlighting that the diagnosis may be overlooked.Dysregulated expression of RUNX1-targets in platelets, including downregulation of the α2subunit (GPIa) of collagen receptor α2β16 or persistent myosin 10 (MYH10) expression,7 havebeen proposed as screening tools to guide diagnosis, although it is at present unknown whetherall FPD/AML patients harbour these defects. Therefore, molecular screening is still required toadequately identify RUNX1 mutation carriers. We report the finding of genetic mosaicism in a patient belonging to a well-characterized FPD/AML pedigree and describe the relationship between molecular and clinical features over a 12-year follow-up.