BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:"\;miR-221 promotes precursor B-cell retention in bone marrow by amplifying the Pi3K-signaling pathway"\; - Dr Georg Petkau\; German Rheumatism Research Centre\, Berlin DTSTART:20170928T100000Z DTEND:20170928T110000Z UID:TALK81021@talks.cam.ac.uk CONTACT:Bobbie Claxton DESCRIPTION:Hematopoietic stem-cells (HSC) and lineage-uncommitted progeni tors are able to home to bone marrow and reconstitute the host with hemato poietic progeny upon transplantation. Expression of the miR221/222 cluster correlates with the ability of lineage uncommitted cells to home to and r eside in bone marrow upon transplantation. Re-expression of miR221 in B-li neage committed\, miR221 non expressing preBI-cells\, induces their previo usly lost capacity to home to bone marrow. We have identified a mechanism\ , whereby miR221 regulates bone marrow retention of miR221 expressing cell s\, by targeting PTEN expression and enhancing PI3K signaling in response to stimulation by the chemokine CXCL12. MiR221-enhanced PI3K signaling lea ds to increased expression of the antiapoptotic protein Bcl2 and increased activation of VLA4 integrins. This activation results in a sustained adh esion to VCAM1 in response to CXCL12 in vitro. Inhibition of miR221-enhan ced PI3K activity abolishes Bcl2-expression\, cellular adhesion in vitro a nd retention of miR221 expressing preBI-cells in bone marrow in vivo. Thes e results suggest a model where the amplification of PI3K signaling by miR 221 could be a general mechanism for bone marrow residence\, shared by nor mal and malignant miR221-expressing hematopoietic cells. LOCATION:Babraham - The Brian Heap Seminar Room END:VEVENT END:VCALENDAR