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Stem Cell Res. 2016 May;16(3):677-81. doi: 10.1016/j.scr.2016.04.007. Epub 2016 Apr 12.

GABP is necessary for stem/progenitor cell maintenance and myeloid differentiation in human hematopoiesis and chronic myeloid leukemia.

Author information

1
Institute of Human Genetics, Hannover Medical School, Hannover, Germany. Electronic address: manukjan.georgi@mh-hannover.de.
2
Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
3
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
4
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

Abstract

Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34(+) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.

KEYWORDS:

CML/chronic myeloid leukemia; GABP; Hematopoietic stem cell; Leukemic stem cell; Transcription factor

PMID:
27100840
DOI:
10.1016/j.scr.2016.04.007
[Indexed for MEDLINE]
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