Normal immature LSK from mice transduced with retrovirus using CombiMag were transplanted intravenously into irradiated mice.
This paper shows the efficiency of CombiMag from OZ Biosciences to allow and enhance transduction of primary haematopoietic LSK cells from mouse with retrovirus.article reference: Blood. 2014 Feb 26.
The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells.
Kobayashi CI1, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T.
Abstract
Just as normal stem cells require niche cells for survival, leukemia-initiating cells (LICs) may also require niche cells for their maintenance. Chronic myeloid
leukemia (CML) is caused by the activity of BCR-ABL, a constitutively
active tyrosine kinase. CML therapy with tyrosine kinase inhibitors
(TKIs) is highly effective; however, due to the persistence of residual
LICs, it is not curative. Several factors are known to support CML LICs,
but purification of LICs and a thorough understanding of their niche
signals have not yet been achieved. Using a CML-like mouse model of
myeloproliferative disease, we demonstrate that CML LICs can be divided
into CD25+FcεRIα- Lineage marker (Lin)- Sca-1+c-Kit+ (F-LSK) cells and CD25-F-LSK cells. The CD25+F-LSK cells had multi-lineage differentiation capacity, with a preference toward cytokine-producing mast cell commitment. Although cells interconverted between CD25-F-LSK and CD25+F-LSK status, the CD25+F-LSK cells exhibited higher LIC capacity. Our findings suggest that IL-2 derived from the microenvironment and CD25 expressed on CML LICs constitute a novel signaling axis. The high levels of CD25 expression in the CD34+CD38- fraction of human CML cells indicate that CD25+ LICs constitute an "LIC-derived niche" that could be preferentially targeted in therapy for CML.
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