International Journal of Hematology

DOI: 10.1007/s12185-018-2514-3 Pages: 652-657

C-terminal RUNX1 mutation in familial platelet disorder with predisposition to myeloid malignancies

1. Masaryk University, Central European Institute of Technology (CEITEC), University Hospital

2. Masaryk University, Department of Internal Medicine, Hematology and Oncology, University Hospital

3. University Hospital, Department of Pediatric Hematology

4. University Hospital, Department of Hematologic Oncology

5. Palacký University, Department of Hematologic Oncology, University Hospital

Correspondence to:
Michael Doubek
Tel: +42 0 532 233 642



Here we report a C-terminal RUNX1 mutation in a family with platelet disorder and predisposition to myeloid malignancies. We identified the mutation c.866delG:p.Gly289Aspfs*22 (NM_001754) (RUNX1 b-isoform NM_001001890; c.785delG:p.Gly262Aspfs*22) using exome sequencing of samples obtained from eight members of a single family. The mutation found in our pedigree is within exon eight and the transactivation domain of RUNX1. One of the affected individuals developed myelodysplastic syndrome (MDS), which progressed to acute myelogenous leukemia (AML). A search for the second hit which led to the development of MDS and later AML in this individual revealed the PHF6 gene variant (exon9:c.872G > A:p.G291E; NM_001015877), BCORL1 (exon3:c.1111A > C:p.T371P; NM_001184772) and BCOR gene variant (exon4:c.2076dupT:p.P693fs; NM_001123383), which appear to be very likely second hits participating in the progression to myeloid malignancy.

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