ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells.

ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells. Haematologica. 2018 Sep 27;: Authors: Portale F, Cricrì G, Bresolin S, Lupi M, Gaspari S, Silvestri D, Russo B, Marino N, Ubezio P, Pagni F, Vergani P, Te Kronnie G, Valsecchi MG, Locatelli F, Rizzari C, Biondi A, Dander E, D'Amico G Abstract B-cell precursor-Acute Lymphoblastic Leukemia modulates the bone marrow niche to become leukemia-supporting and chemoprotective by reprogramming the stromal microenvironment. New therapies targeting the leukemia/stroma interplay can be instrumental to improve disease outcome. We identified ActivinA, a TGF-β family member, with a well-described promoting role in several solid malignancies, as a new potentially targetable leukemia-favoring factor. ActivinA resulted overexpressed in the leukemic bone marrow and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells. Moreover, mesenchymal stromal cells isolated from bone marrow of leukemic patients showed an intrinsic ability to secrete higher amounts of ActivinA compared to their normal counterpart. The pro-inflammatory leukemic bone marrow microenvironment synergized with leukemic cells to induce stromal-derived ActivinA. Gene expression analysis of ActivinA-treated leukemic cells showed that this protein was able to significantly influence motility-associated pathways. Inter...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research