JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis

Blood - Tập 108 Số 5 - Trang 1652-1660 - 2006
Catherine Lacout1, Didier F. Pisani2,1, M Tulliez2,1, Françoise Moreau Gachelin2,1, William Vainchenker2,1, Jean‐Luc Villeval2,1
1Institut National de la Sante et de la Recherche Medicale (INSERM) U790, Université Paris XI, Institut Gustave Roussy (IGR), Villejuif, France.
2INSERM U528, Institut Curie, Université Paris V, Paris, France

Tóm tắt

A JAK2V617F mutation is frequently found in several BCR/ABL-negative myeloproliferative disorders. To address the contribution of this mutant to the pathogenesis of these different myeloproliferative disorders, we used an adoptive transfer of marrow cells transduced with a retrovirus expressing JAK2V617F in recipient irradiated mice. Hosts were analyzed during the 6 months after transplantation. For a period of 3 months, mice developed polycythemia, macrocytosis and usually peripheral blood granulocytosis. Transient thrombocytosis was only observed in a low-expresser group. All mice displayed trilineage hyperplasia in marrow and spleen along with an amplification of myeloid and erythroid progenitor cells and a formation of endogenous erythroid colonies. After 3 to 4 months, polycythemia regressed, abnormally shaped red blood cells and platelets were seen in circulation, and a deposition of reticulin fibers was observed in marrow and spleen. Development of fibrosis was associated with anemia, thrombocytopenia, high neutrophilia, and massive splenomegaly. These features mimic human polycythemia vera and its evolution toward myelofibrosis. This work demonstrates that JAK2V617F is sufficient for polycythemia and fibrosis development and offers an in vivo model to assess novel therapeutic approaches for JAK2V617F-positive pathologies. Questions remain regarding the exact contribution of JAK2V617F in other myeloproliferative disorders.

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Blood

Tập 108 Số 5

1652-1660

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