In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 46.13-46.13
Abstract:
Although it is generally acknowledged that cytokines regulate normal hematopoiesis in an autocrine/paracrine fashion, their possible role in chronic myeloid leukemia (CML) and resistance to imatinib mesylate (IM) treatment remain poorly investigated. Here, we report that CD34(+) progenitors from CML patients at diagnosis are selectively targeted by the cytokine/alarmin IL-33. Indeed, CML CD34(+) progenitors up-regulate their cell surface expression of the IL-33-specific receptor chain ST2, proliferate and produce cytokines in response to IL-33, conversely to CD34(+) cells from healthy individuals. Moreover, ST2 overexpression is normalized following IM therapy, while IL-33 counteracts in-vitro IM-induced growth arrest in CML CD34(+) progenitors via re-activation of the STAT5 pathway. Clinically, CML is associated with high circulating levels of soluble ST2, commonly used as a functional signature of IL-33 signaling in vivo. Taken together, our results support the hypothesis that the IL-33/ST2 pathway facilitates Bcr/Abl-induced leukemogenesis and contributes to IM resistance in CML patients.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.46.13
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5