An insight on the role of genetic testing of RUNX1: A key transcriptional gene in familial platelet disorder with predisposition to acute myeloid leukemia

Abstract

Background: Familial platelet disorder (FPD) with predisposition to acute myeloid leukemia (AML) is an autosomal dominant disease of the hematopoietic system that is caused by heterozygous mutations in RUNX1 gene. RUNX1 is frequently involved in the pathogenesis of sporadic leukemia and myelodysplastic syndromes, through acquired chromosome rearrangements and point mutations. Along with intensive chemotherapy regimens, novel targeted therapies are required to increase the surveillance rate in childhood AML. Case report: This study highlights importance of genetic counselling and genetic tests to detect FPD/AML in a 4-year-old diagnosed with AML along with a family history of myeloid malignancies. Germline testing confirmed a pathogenic variant in RUNX1 gene. Patient underwent myeloablative conditioning with a successful allogenic bone marrow transplant (BMT). The mutation specific test for the variant in RUNX1 was found negative. Conclusion: Genetic counselling helped in identifying FPD in the family, and, to identify the right donor for BMT.

Keywords

• FPD/AML
• RUNX1
• Germline test
• Mutation specific test
• Genetic counselling