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

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

Author information

1
Department of Pharmacology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.

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.

PMID:
22371173
PMCID:
PMC3436240
DOI:
10.3324/haematol.2011.059113
[Indexed for MEDLINE]
Free PMC Article

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