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

Abstract

The JAK2V617F mutation has been found in most cases of Phnegative 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. ©2012 Ferrata Storti Foundation.