Abstract
In the present study, we report that media conditioned by polycythemia vera (PV) CD3+ cells promote BFU-E and CFU-Mk colony formation by both cord blood and PV peripheral blood CD34+ cells in the absence of exogenous cytokines and promoting megakaryocyte proplatelet formation. CD3+ cells constitutively produce elevated levels of IL-11, while stimulation with the addition of phytohemagglutinin (PHA) increased GM-CSF levels in most of the patients with PV. Anti-IL-11-neutralizing antibody partially inhibited the formation of BFU-E and CFU-Mk colonies promoted by PV CD3+ cell-conditioned media. Although IL-11 is not produced by normal T cells, real-time PCR and flow cytometric analysis showed that IL-11 was upregulated in the CD3+ cells of most PV patients as compared to normal CD3+ cells. In addition, a greater percentage of BFU-E colonies formed by PV CD34+ cells in the presence of PV CD3+ cell-conditioned media alone were JAK2V617F-positive as compared with that induced by EPO. We conclude that dysregulated production of soluble growth factor(s), including IL-11 and GM-CSF by PV T cells, contributes to the in vitro formation of erythroid colonies in the absence of exogenous cytokines by PV CD34+ cells and likely plays a role in sustaining hematopoiesis in PV.
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Acknowledgements
This study was supported by grants from the Department of Defense (MP048007 to MX) the Myeloproliferative Disorders Foundation (to MX and RH) and National Cancer Institute (1P01CA108671 to RH).
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Ishii, T., Zhao, Y., Shi, J. et al. T cells from patients with polycythemia vera elaborate growth factors which contribute to endogenous erythroid and megakaryocyte colony formation. Leukemia 21, 2433–2441 (2007). https://doi.org/10.1038/sj.leu.2404899
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DOI: https://doi.org/10.1038/sj.leu.2404899
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