title: Role of chemokines and their receptors in chronic lymphocytic leukemia: function in microenvironment and targeted therapy.
abstract: Chemokines produced in distinct tissue microenvironments sustain migration of mature lymphocytes in lymphoglandula. Chemokine receptors expressed on chronic lymphocytic leukemia (CLL) cells regulate the migration of the leukemia cells within the bone marrow (BM), lymphoid organs in collaboration with chemokines. Chemokines form a pro-survival circuitry by regulating leukocyte trafficking, maintaining extended lymphocyte survival. Therefore, chemokines in tumor cell-microenvironment interactions represent a target for treatment of CLL. AMD3100 disrupts the CLL/microenvironment interactions and influences CXCL12/CXCR4 survival signaling. Fostamatinib, ibrutinib, and GS-1101 as B-cell receptor (BCR)-related kinase inhibitors inhibit BCR- and chemokine-receptor-signal-regulated kinase and have a good clinical response in CLL. Lenalidomide, sorafenib, and dasatinib are other additional drugs associated with chemokine in microenvironment. Inhibiting signaling through chemokine and microenvironment associated signaling are emerging as innovative therapeutic targets in CLL. In this article, we reviewed the role of chemokines in CLL microenvironment and novel therapeutics targeting CLL microenvironment.
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Han
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000631:Aminopyridines; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002986:Clinical Trials as Topic; D000080027:Cyclams; D000069439:Dasatinib; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009025:Morpholines; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077157:Sorafenib; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D059016:Tumor Microenvironment
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D009025:Morpholines; D010078:Oxazines; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011687:Purines; D011725:Pyridines; D011743:Pyrimidines; D052999:Quinazolinones; D019718:Receptors, CXCR4; D013844:Thiazoles; D009536:Niacinamide; D013792:Thalidomide; D000077157:Sorafenib; D000077269:Lenalidomide; D000069439:Dasatinib; C088327:plerixafor; C523665:fostamatinib; C552946:idelalisib
keywords: chemokines; chemokines receptors; chronic leukemia lymphoma; microenvironment; targeted therapy