Erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a myeloproliferative disease in mice

Haematologica. 2012 Sep;97(9):1389-93. doi: 10.3324/haematol.2011.059113. Epub 2012 Feb 27.

Abstract

The JAK2V617F mutation has been found in most cases of Ph-negative myeloproliferative neoplasms. Recent studies have shown that expression of Jak2V617F in the hematopoietic compartment causes marked expansion of erythroid progenitors and their transformation to cytokine-independence. To determine if erythroid progenitors are the target cells for induction and propagation of Jak2V617F-evoked myeloproliferative neoplasm, we used a conditional Jak2V617F knock-in mouse and an erythroid-lineage specific EpoRCre line. Erythroid-specific expression of heterozygous or homozygous Jak2V617F resulted in a polycythemia-like phenotype characterized by increase in hematocrit and hemoglobin, increased red blood cells, erythropoietin-independent erythroid colonies and splenomegaly. Transplantation of Jak2V617F-expressing erythroid progenitors from the diseased mice into secondary recipients could not propagate the disease. Our results suggest that erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a polycythemia-like disease in a gene-dose dependent manner. Jak2V617F mutation, however, does not confer leukemia stem cell-like properties to erythroid progenitors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Lineage*
  • Cells, Cultured
  • Erythroid Precursor Cells / metabolism*
  • Erythroid Precursor Cells / pathology
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Integrases / metabolism
  • Janus Kinase 2 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Myeloproliferative Disorders / complications
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology*
  • Polycythemia / etiology*
  • Polycythemia / pathology
  • Receptors, Erythropoietin / physiology*
  • Signal Transduction

Substances

  • Receptors, Erythropoietin
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Cre recombinase
  • Integrases