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- Title
In vitro expansion of CD34<sup>+</sup>CD38<sup>−</sup> cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.
- Authors
Sakashita, K; Kato, I; Daifu, T; Saida, S; Hiramatsu, H; Nishinaka, Y; Ebihara, Y; Ma, F; Matsuda, K; Saito, S; Hirabayashi, K; Kurata, T; Uyen, L T N; Nakazawa, Y; Tsuji, K; Heike, T; Nakahata, T; Koike, K
- 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.
- Subjects
HEMATOPOIETIC growth factors; MONOCYTIC leukemia; TRANSPLANTATION of organs, tissues, etc.; IMMUNODEFICIENCY; THERAPEUTICS; PATIENTS
- Publication
Leukemia (08876924), 2015, Vol 29, Issue 3, p606
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2014.239