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Expansion of normal and leukemic human hematopoietic stem/progenitor cells requires Rac-mediated interaction with stromal cells

Rozenveld-Geugien, Marjan, Baas, Inge O., van Gosliga, Djoke, Vellenga, Edo, Schuringa, Jan Jacob·2007·Experimental Hematology
DOI 10.1016/j.exphem.2007.02.006
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Abstract

Objective To determine the involvement of Rac signaling in self-renewal and expansion on bone marrow stroma of normal CD34+ cells vs leukemic CD34+ cells from acute myeloid leukemia (AML) patients. Materials and methods Rac signaling was modulated by retroviral introduction of Racl-N17, Racl-V12, or by using the Rac inhibitor NSC23766. In long-term MS5 cocultures (leukemic) expansion, migration, adhesion, and presence of stem/progenitor cells were monitored in both normal as well as leukemic CD34+ cells. Results Inhibition of Rac signaling impaired migration and adhesion of cord blood (CB) CD34+ cells on MS5 stroma. Long-term inhibition of Rac during a 5-week coculture period on stroma prevented association of hematopoietic progenitors with the bone marrow stromal cells and resulted in a dramatic decrease in the primitive stem cell frequency (long-term culture-initiating cell) in a dose-dependent manner. Many of these phenotypes were reversed in the presence of activated Racl-V12, including improved migration toward, and association with, MS5 cells. CD34+ AML cells were characterized by elevated levels of Rac activity (five of seven patients) and enhanced migration and adhesion to MS5 bone marrow stroma as compared to CB CD34+ cells. A dramatic decrease was observed in the formation of leukemic cobblestone area-forming cells as well as strongly diminished clonal expansion in the presence of the Rac inhibitor NSC23766. Conclusion Our data indicate that Rac signal transduction…

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Metadata

Authors
Rozenveld-Geugien, M., Baas, I. O., van Gosliga, D., Vellenga, E., & Schuringa, J. J.
Venue
Experimental Hematology
Publisher
Elsevier BV
Published
2007-05
Volume
35
Issue
5
Pages
782-792
ISSN
0301-472X
DOI
10.1016/j.exphem.2007.02.006
Cited by
19
References
3
Language
en
Licence

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CoChat. (2026). Citation check: Expansion of normal and leukemic human hematopoietic stem/progenitor cells requires Rac-mediated interaction with stromal cells. https://app.cochat.ai/papers/10.1016/j.exphem.2007.02.006
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Rozenveld-Geugien, M., Baas, I. O., van Gosliga, D., Vellenga, E., & Schuringa, J. J. (2007). Expansion of normal and leukemic human hematopoietic stem/progenitor cells requires Rac-mediated interaction with stromal cells. Experimental Hematology. https://doi.org/10.1016/j.exphem.2007.02.006