High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression
Nicole L Wittwer, Gabriela Brumatti, Ceilidh Marchant, Jarrod J Sandow, Melanie K Pudney, Mara Dottore, Richard J D'Andrea, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw
BLOOD ADVANCES | AMER SOC HEMATOLOGY | Published : 2017
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations. This was as..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Cancer Australia/Leukaemia Foundation
This work was supported by project grants from the National Health and Medical Research Council (1048071) (P.G.E. and H.S.R.), (1081376) (G.B.), (1071897) (A.F.L.); and the Cancer Australia/Leukaemia Foundation (1010336) (A.F.L. and H.S.R.). H.S.R. is supported by the Peter Nelson Leukaemia Research Fund. N.L.W. was supported by a Leukaemia Foundation of Australia PhD scholarship. G.B. is supported by a Victorian Cancer Agency MidCareer fellowship. This work was made possible through Victorian State Government Operational Infrastructure Support, and L.E.W. Carty Charitable Fund and Ian Rollo Currie Estate Foundation for infrastructure support.