First Author | Akada H | Year | 2012 |
Journal | Haematologica | Volume | 97 |
Issue | 9 | Pages | 1389-93 |
PubMed ID | 22371173 | Mgi Jnum | J:231133 |
Mgi Id | MGI:5766886 | Doi | 10.3324/haematol.2011.059113 |
Citation | Akada H, et al. (2012) Erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a myeloproliferative disease in mice. Haematologica 97(9):1389-93 |
abstractText | 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. |