Expression of JAK2-V617F Kinase Profoundly Dysregulates the Functional Properties of β1 Integrins on Myeloid Cells

Introduction: Deregulated signal transduction pathways driven by the constitutively active JAK2-V617F kinase, play a central role in pathogenesis of the classical Philadelphia negative myeloproliferative neoplasms (MPNs). Polycythemia vera, essential thrombocythemia and primary myelofibrosis are characterized by clonal proliferation of myeloid cells and development of inflammatory syndrome (CRP elevation, fever, high proinflammatory cytokine plasma levels) particularly, in advanced phases of the disease. Integrins are heterodimeric cell surface receptors that mediate a wide range of anchorage dependent events fundamentally essential in adhesion and mobility of leukocytes during inflammatory states. An intricate network of intracellular signaling pathways triggers the activation of intergins by allosteric conformational changes and/or by altering lateral mobility to increase receptor clustering.