Role of chemokines and their receptors in chronic lymphocytic leukemia

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.

Keywords: :

• chronic leukemia lymphoma
• microenvironment
• chemokines
• chemokines receptors
• targeted therapy

10.4161/cbt.26607

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This study was supported by National Natural Science Foundation of China (30971296, 81170488, 81370657), Natural Science Foundation of Jiangsu Province (BK2010584), Key Projects of Health Department of Jiangsu Province (K201108), Jiangsu Province’s Medical Elite Program (RC2011169), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (JX10231801), National Public Health Grand Research Foundation (201202017), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, Jiangsu Province Higher Education Institute Foundation of Science and Technology Innovation Team Program, and the Project for State Key Clinical Department construction.