In vitro expansion of CD34+CD38− cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03

AUTHORS

K Sakashita, I Kato, T Daifu, S Saida, H Hiramatsu, Y Nishinaka, Y Ebihara, F Ma, K Matsuda, S Saito, K Hirabayashi, T Kurata, L T N Uyen, Y Nakazawa, K Tsuji, T Heike, T Nakahata, K Koike

ABSTRACT

Using serum-containing culture, we examined whether AGM-S3 stromal cells, alone or in combination with hematopoietic growth factor(s), stimulated the proliferation of CD34(+) cells from patients with juvenile myelomonocytic leukemia (JMML). AGM-S3 cells in concert with stem cell factor plus thrombopoietin increased the numbers of peripheral blood CD34(+) cells to approximately 20-fold of the input value after 2 weeks in nine JMML patients with either PTPN11 mutations or RAS mutations, who received allogeneic hematopoietic transplantation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) also augmented the proliferation of JMML CD34(+) cells on AGM-S3 cells. The expansion potential of CD34(+) cells was markedly low in four patients who achieved spontaneous hematological improvement. A large proportion of day-14-cultured CD34(+) cells were negative for CD38 and cryopreservable. Cultured JMML CD34(+)CD38(-) cells expressed CD117, CD116, c-mpl, CD123, CD90, but not CXCR4, and formed GM and erythroid colonies. Day-7-cultured CD34(+) cells from two of three JMML patients injected intrafemorally into immunodeficient mice stimulated with human GM-CSF after transplantation displayed significant hematopoietic reconstitution. The abilities of OP9 cells and MS-5 cells were one-third and one-tenth, respectively, of the value obtained with AGM-S3 cells. Our culture system may provide a useful tool for elucidating leukemogenesis and for therapeutic approaches in JMML. More... »

PAGES

606

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2014.239

DOI

http://dx.doi.org/10.1038/leu.2014.239

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027393552

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25102944


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