The hematopoietic stem cell compartment of JAK2V617F-positive myeloproliferative disorders is a reflection of disease heterogeneity

Blood. 2008 Sep 15;112(6):2429-38. doi: 10.1182/blood-2008-02-137877. Epub 2008 Jul 8.


The JAK2V617F somatic point mutation has been described in patients with myeloproliferative disorders (MPDs). Despite this progress, it remains unknown how a single JAK2 mutation causes 3 different MPD phenotypes, polycythemia vera (PV), essential thrombocythemia, and primitive myelofibrosis (PMF). Using an in vivo xenotransplantation assay in nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice, we tested whether disease heterogeneity was associated with quantitative or qualitative differences in the hematopoietic stem cell (HSC) compartment. We show that the HSC compartment of PV and PMF patients contains JAK2V617F-positive long-term, multipotent, and self-renewing cells. However, the proportion of JAK2V617F and JAK2 wild-type SCID repopulating cells was dramatically different in these diseases, without major modifications of the self-renewal and proliferation capacities for JAK2V617F SCID repopulating cells. These experiments provide new insights into the pathogenesis of JAK2V617F MPD and demonstrate that a JAK2 inhibitor needs to target the HSC compartment for optimal disease control in classical MPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Janus Kinase 2 / genetics*
  • Mice
  • Mice, SCID
  • Mutation, Missense
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology*
  • Phenotype
  • Polycythemia Vera / genetics
  • Polycythemia Vera / pathology
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / pathology
  • Transplantation, Heterologous


  • Janus Kinase 2