Research Information System
LEUKEMIA, vol.21, no.12, pp.2433-2441, 2007 (SCI-Expanded)
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, realtime 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.