title: T cells from patients with polycythemia vera elaborate growth factors which contribute to endogenous erythroid and megakaryocyte colony formation.
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.
authors: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors: T
authors: T
authors: Ishii
authors: Y
authors: Y
authors: Zhao
authors: J
authors: J
authors: Shi
authors: S
authors: S
authors: Sozer
authors: R
authors: R
authors: Hoffman
authors: M
authors: M
authors: Xu
mesh_terms: 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*
chemical_list: 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