Klin Padiatr 2011; 223 - A28
DOI: 10.1055/s-0031-1277089

GATA1s exerts fetal stage-specific oncogenic effects in hematopoietic stem and progenitor cells

A Maroz 1, C Hennig 2, D Reinhardt 1, JH Klusmann 1
  • 1Pediatric Oncology and Hematology, Hannover Medical School
  • 2Pediatric Pneumology. Allergology and Immunology, Hannover Medical School

Introduction: Mutations of the hematopoietic transcription factor GATA1, leading to expression of a shorter N-terminal truncated protein (GATA1s) are associated with transient leukemia (TL) and acute megakaryoblastic leukemia (AMKL) in children with Down syndrome. However, the consequences of GATA1s expression in synergy with fetal background in human hematopoietic stem and progenitor cells (HSPCs) remain unknown.

Methods: Colony-forming capacity and multilineage differentiation of GATA1/GATA1s transduced human CD34+ HSPCs from fetal liver (FL), cord blood (CB) and adult peripheral blood (G-CSF-mobilized) were investigated.

Results: Overexpression of mutated GATA1s induced hyperproliferation of FL and to a smaller extend in CB megakaryocytic progenitor cells. In methylcellulose colony-forming assays GATA1s transduced FL HSPCs gave rise to atypical colonies, consisting of basophilic or eosinophilic progenitors. Overexpression of either GATA1 or GATA1s blocked myeloid differentiation of HSPCs.

Conclusion: GATA1s alters hematopoietic differentiation and increases MPC proliferation in concert with fetal but not neonatal or adult background.