title: Interactions between bone marrow stromal microenvironment and B-chronic lymphocytic leukemia cells: any role for Notch, Wnt and Hh signaling pathways?
abstract: B-cell chronic lymphocytic leukemia (CLL), which is the most common lymphoproliferative disorder, displays characteristics consistent with a defect in programmed cell death and exhibit prolonged survival of affected cells in vivo. When recovered from peripheral blood or lymphoid tissues of patients and cultured in vitro, CLL malignant cells rapidly undergo spontaneous apoptosis. CLL B-cells co-culture with different adherent cell types, collectively referred to as stromal cells, induces leukemia cell survival, migration, and drug resistance. In addition, such survival-promoting microenvironments can rescue leukemia cells from cytotoxic therapy, giving way to disease relapse. Quite surprisingly considering that many anti-cancer drugs, including γ-secretase inhibitors, Cyclopamine and Quercetin, were reported to block Notch, Wnt, and Hedgehog anti-apoptotic signaling pathways respectively, the link between the latter anti-apoptotic pathways and bone marrow stromal cells in CLL has been pointed out only recently. Data concerning the pathogenesis of CLL have been critically reviewed in regards to the growing body of evidence indicating deregulations of Notch, Wnt and Hedgehog anti-apoptotic signaling pathways in the stromal microenvironment of affected cells.
authors.affiliation: Department of Neurological Sciences (DNNMMS), University of Verona, Verona, Italy. Paul.seke@gmail.com
authors.forename: Paul Faustin
authors.initials: PF
authors.lastname: Seke Etet
authors.forename: Lorella
authors.initials: L
authors.lastname: Vecchio
authors.forename: Armel Hervé
authors.initials: AH
authors.lastname: Nwabo Kamdje
mesh_terms: D001853:Bone Marrow / Q000378:metabolism; D060833:Cellular Microenvironment; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072086:Smoothened Receptor; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D053823:Hedgehog Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor