Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects

Jon P. Connelly, Erika M. Kwon, Yongxing Gao, Niraj S. Trivedi, Abdel G. Elkahloun, Marshall S. Horwitz, Linzhao Cheng, P. Paul Liu

Research output: Contribution to journalArticle

Abstract

Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomaldominant disease of the hematopoietic system that is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. No suitable animal models exist for FPD/AML, as Runx1+/-mice and zebra fish do not develop bleeding disorders or leukemia. Here we derived induced pluripotent stem cells(iPSCs) from 2 patientsina family with FPD/AML, and found that the FPD iPSCs display defects in megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in 1 FPD iPSC line through gene targeting, which led to normalization of megakaryopoiesis of the iPSCs in culture. Our results demonstrate successful in vitro modeling of FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible for megakaryopoietic defects in FPD patients.

Original languageEnglish (US)
Pages (from-to)1926-1930
Number of pages5
JournalBlood
Volume124
Issue number12
DOIs
StatePublished - Sep 18 2014

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Connelly, J. P., Kwon, E. M., Gao, Y., Trivedi, N. S., Elkahloun, A. G., Horwitz, M. S., Cheng, L., & Liu, P. P. (2014). Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects. Blood, 124(12), 1926-1930. https://doi.org/10.1182/blood-2014-01-550525