title: The CLL cell microenvironment.
abstract: Cross talk between CLL cells and accessory stromal cells in specialized tissue microenvironments, such as the secondary lymphoid organs, favors CLL progression by promoting malignant B cell growth and drug resistance. Disrupting the cross talk between CLL cells and their milieu is an attractive, novel strategy for treating CLL patients. This chapter summarizes current knowledge about cellular and molecular interactions between CLL cells and their supportive tissue microenvironment and the therapeutic targets that are emerging, focusing on the CXCR4-CXCL12 axis and small molecule inhibitors that are targeting the B cell receptor-associated kinases SYK, BTK, and PI3Kδ. Clinically relevant aspects of these new therapeutics will be discussed, along with an outlook into future biologically oriented therapeutic strategies. The rapid progress in dissecting the CLL microenvironment and the promising early results of these new targeted treatments in CLL indicate that CLL has become a role model for microenvironment-dependent cancers.
authors.affiliation: Unit 428, Department of Leukemia, The University of Texas MD Anderson Cancer Center, 301402, Houston, TX, 77230-1402, USA, jaburger@mdanderson.org.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D002448:Cell Adhesion; D002465:Cell Movement; D060833:Cellular Microenvironment; D006801:Humans; D039041:Integrin alpha4beta1 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology; D000072377:Syk Kinase
chemical_list: D039041:Integrin alpha4beta1; D047908:Intracellular Signaling Peptides and Proteins; D019707:Receptors, Chemokine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase