Toward a therapeutic reduction of imatinib refractory myeloproliferative neoplasm-initiating cells

Jak2V617F myeloproliferative neoplasm stem cells and interferon-alpha

The myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoiesis that arise as a result of aberrant activation of tyrosine kinases and result in the proliferation and accumulation of mature myeloid cells in the blood, bone marrow and spleen. The prototypical MPN, chronic myeloid leukemia (CML) is caused by constitutive activation of ABL kinase occurring as a result of the BCR-ABL f...

Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm

Our understanding of inflammation's role in the pathogenesis of myeloproliferative neoplasm (MPN) is evolving. The impact of chronic inflammation, a characteristic feature of MPN, likely goes far beyond its role as a driver of constitutional symptoms. An inflammatory response to the neoplastic clone may be responsible for some pathologic aspects of MPN. Moreover, JAK2V617F mutated hematopoietic...

Hypothetical Atopic Dermatitis-Myeloproliferative Neoplasm Syndrome

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopo...

Low-dose methotrexate in myeloproliferative neoplasm models.

JAK2 inhibition has different therapeutic effects according to myeloproliferative neoplasm development in mice

JAK2 inhibition therapy is used to treat patients suffering from myeloproliferative neoplasms (MPN). Conflicting data on this therapy are reported possibly linked to the types of inhibitors or disease type. Therefore, we decided to compare in mice the effect of a JAK2 inhibitor, Fedratinib, in MPN models of increasing severity: polycythemia vera (PV), post-PV myelofibrosis (PPMF) and rapid post...