A de novo germline RUNX1 variant preceding development of concurrent T-lymphoblastic leukemia and myelodysplastic syndrome

Leuk Lymphoma. 2024 Sep;65(9):1357-1361. doi: 10.1080/10428194.2024.2347577. Epub 2024 May 11.

Abstract

Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.

Keywords: MDS; RUNX1 variant; T-ALL.

Publication types

  • Case Reports

MeSH terms

  • Blood Coagulation Disorders, Inherited
  • Blood Platelet Disorders / complications
  • Blood Platelet Disorders / diagnosis
  • Blood Platelet Disorders / genetics
  • Child
  • Core Binding Factor Alpha 2 Subunit* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute
  • Male
  • Myelodysplastic Syndromes* / diagnosis
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / therapy

Substances

  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human

Supplementary concepts

  • Platelet Disorder, Familial, with Associated Myeloid Malignancy