University of Cambridge > Talks.cam > Babraham Seminar > "miR-221 promotes precursor B-cell retention in bone marrow by amplifying the Pi3K-signaling pathway"

"miR-221 promotes precursor B-cell retention in bone marrow by amplifying the Pi3K-signaling pathway"

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Hematopoietic stem-cells (HSC) and lineage-uncommitted progenitors are able to home to bone marrow and reconstitute the host with hematopoietic progeny upon transplantation. Expression of the miR221/222 cluster correlates with the ability of lineage uncommitted cells to home to and reside in bone marrow upon transplantation. Re-expression of miR221 in B-lineage committed, miR221 non expressing preBI-cells, induces their previously lost capacity to home to bone marrow. We have identified a mechanism, whereby miR221 regulates bone marrow retention of miR221 expressing cells, by targeting PTEN expression and enhancing PI3K signaling in response to stimulation by the chemokine CXCL12 . MiR221-enhanced PI3K signaling leads to increased expression of the antiapoptotic protein Bcl2 and increased activation of VLA4 integrins. This activation results in a sustained adhesion to VCAM1 in response to CXCL12 in vitro. Inhibition of miR221-enhanced PI3K activity abolishes Bcl2-expression, cellular adhesion in vitro and retention of miR221 expressing preBI-cells in bone marrow in vivo. These results suggest a model where the amplification of PI3K signaling by miR221 could be a general mechanism for bone marrow residence, shared by normal and malignant miR221-expressing hematopoietic cells.

This talk is part of the Babraham Seminar series.

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