Blood: The role of the ECM-integrator receptor axis in the abnormal proliferation of primary bone marrow fibrosis macronuclear cells

Excessive accumulation of extracellular matrix (ECM) is a marker in primary bone marrow fibrosis (PMF) bone marrow (BM) environmentsBecause cells have the ability to adhere to the surrounding ECM through the integration receptor, Matsuura et alhave validated the hypothesis that ECM-integrator receptor axis abnormalities lead to the growth of JAK2V617FPMF bone marrow macronuclear cellsECM protein fibrous protein (FN) secreted by bone marrow matrix cells in PMF patients is associated with fibrosis and the severity of diseasein this study, the researchers found that Vav1-hJAK2V617F genetically modified mice (JAK2V617F) had high LEVELs of BM FN associated with macronucleosis and fibrosisIn addition, compared to wild-type controls, the expression of a55 subunits (the main FN receptor on the macronuclear cells) of the a5b1 integrator (the main FN receptor on the macronuclear cells) in themice of the giant nuclear cells of the jak2V617F increased, enhancing the adhesion to FNinhibition antibodies with a5 subunits can block its adhesion to FN, effectively reducing the proportion of CD41plusJAK2V617FConsistent with the findings in mice, the expression levels of a5 subkeys from the patient's JAK2V617F-
giant nuclear cells also increased, and a5 sub-cells neutralized antibodies also reduced the adanication of FN and macronuclear cells from CD34plus cells , this study reveals an unprecedented contribution of FN-a5b1 integrators to the proliferation of macronuclear cells in JAK2V617F plus PMF