Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs

Abstract

The chimeric oncogene Bcr-Abl is known to induce autonomous motility of leukemic cells. We show here that p210

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

“…Results are obtained by counting the number of migrating cells in the ECM gel [163]. Several authors have used the transwell chamber assay in 3D matrix for testing invasion ability of leukemia cells [164,165]. This method was later refined, by observing leukemia cell motility in 3D Transwell with time-lapse microscopy.…”

Niche Wnt5a regulates the actin cytoskeleton during regeneration of hematopoietic stem cells

“…The GTPase-dependent actin regulatory pathway has been described mostly to affect BCR-ABL p210 -driven leukemogenesis, which, in contrast to , comprises the Bcr guanine exchange domain (Tala et al, 2013). It has been shown that RAC1 deficiency depletes BCR-ABL p210 progenitors (Sengupta et al, 2010), and that the RAC1 and CDC42 exchange factor VAV drives leukemogenic proliferation and survival (Chang et al, 2012), as well as motility (Daubon et al, 2008). These studies and our findings suggest that coupling of small GTPase signals to actin polarization, which is required for directed migration may be a target to reduce leukemogenesis or to prevent reengraftment of leukemia after therapy, not only as has been suggested for BCR-ABL p210 (Thomas et al, 2007) but also for BCR-ABL p185 .…”

p210Bcr−Abl desensitizes Cdc42 GTPase signaling for SDF-1α-directed migration in chronic myeloid leukemia cells

“…guanine nucleotide exchange factor (GEF) activity in hematopoietic BaF3 cells (Harnois et al, 2003;Daubon et al, 2008). However, RhoA activity was almost undetectable in BM-derived Ph( þ ) primary cells (data not shown).…”

“…BcrÀAbl for Rac1 stimulation (Bassermann et al, 2002;Daubon et al, 2008). In addition, phosphorylation and activation of Vav1, induced by SDF-1a, controls the chemotactic response in human primary lymphocytes (Vicente-Manzanares et al, 2005).…”

“…BcrÀAbl activates RhoA through its Dblhomology domain in the Bcr region, and its PTK located in the Abl region phosphorylates Vav1 for Rac1 activation (Daubon et al, 2008). Vav1, known as a proto-oncogene, is predominantly expressed in hematopoietic cells (Matsuguchi et al, 1995;Hornstein et al, 2004), and tyrosine phosphorylation of Vav1 by p210…”