T cells from patients with polycythemia vera elaborate growth factors which contribute to endogenous erythroid and megakaryocyte colony formation

Leukemia. 2007 Dec;21(12):2433-41. doi: 10.1038/sj.leu.2404899. Epub 2007 Aug 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cells, Cultured / metabolism
  • Colony-Forming Units Assay
  • Culture Media, Conditioned / pharmacology
  • Erythroid Precursor Cells / drug effects
  • Erythroid Precursor Cells / pathology*
  • Erythropoietin / pharmacology
  • Fetal Blood / cytology
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Hematopoiesis / drug effects
  • Hematopoietic Cell Growth Factors / biosynthesis*
  • Hematopoietic Cell Growth Factors / pharmacology
  • Humans
  • Interleukin-11 / biosynthesis
  • Janus Kinase 2 / genetics
  • Megakaryocytes / drug effects
  • Megakaryocytes / pathology*
  • Mutation, Missense
  • Phytohemagglutinins / pharmacology
  • Polycythemia Vera / genetics
  • Polycythemia Vera / pathology*
  • T-Lymphocytes / metabolism*

Substances

  • Culture Media, Conditioned
  • Hematopoietic Cell Growth Factors
  • IL11 protein, human
  • Interleukin-11
  • Phytohemagglutinins
  • Erythropoietin
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • JAK2 protein, human
  • Janus Kinase 2