T cells from patients with polycythemia vera elaborate growth factors which contribute to endogenous erythroid and megakaryocyte colony formation.
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.
Ishii
T
T
Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Zhao
Y
Y
Shi
J
J
Sozer
S
S
Hoffman
R
R
Xu
M
M
D002478:Cells, Cultured / Q000378:metabolism; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis; D053614:Janus Kinase 2 / Q000235:genetics; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology*; D020125:Mutation, Missense; D010835:Phytohemagglutinins / Q000494:pharmacology; D011087:Polycythemia Vera / Q000235:genetics / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016298:Hematopoietic Cell Growth Factors; C508611:IL11 protein, human; D017370:Interleukin-11; D010835:Phytohemagglutinins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2