Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia

• Published in: International journal of molecular sciences Vol. 18; no. 8; p. 1824
• Main Authors: Mukaida, Naofumi, Tanabe, Yamato, Baba, Tomohisa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.08.2017; MDPI
• Subjects: Abl protein; Animals; BCR protein; Bone marrow; Bone Marrow - metabolism; CCL3; Cells (biology); Chemokines; Chemokines - metabolism; Chronic myeloid leukemia; Conductors; Crosstalk; Cues; CXCL12; CXCL12 protein; CXCR4; Fusion protein; Genetic crosses; Hematopoiesis - genetics; hematopoietic progenitor cell; hematopoietic stem cell; Hematopoietic Stem Cells - metabolism; Homology; Humans; Kinases; Leukemia; leukemia stem cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - etiology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Mechanical stimuli; Microenvironments; Myeloid leukemia; Neoplastic Stem Cells - metabolism; niche; Oxygen tension; Progenitor cells; Progeny; Protein Binding; Protein-tyrosine kinase; Receptors, Chemokine - metabolism; Review; Shear stress; Signal Transduction; Stem Cell Niche; Stem cell transplantation; Stem cells; Tumor Microenvironment; Tyrosine; leukemia stem cell; CXCL12; CCL3; hematopoietic stem cell; CXCR4; hematopoietic progenitor cell; niche
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18081824

All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments. Fusion between breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog (ABL)-1 gene gives rise to BCR-ABL protein with a constitutive tyrosine kinase activity and transforms HSCs and/or hematopoietic progenitor cells (HPCs) into disease-propagating leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). LSCs can self-renew, proliferate, and differentiate under the influence of the signals delivered by bone marrow microenvironments including niche, as HSCs can. Thus, the interaction with bone marrow microenvironments is indispensable for the initiation, maintenance, and progression of CML. Moreover, the crosstalk between LSCs and bone marrow microenvironments can contribute to some instances of therapeutic resistance. Furthermore, evidence is accumulating to indicate the important roles of bone marrow microenvironment-derived chemokines. Hence, we will herein discuss the roles of chemokines in CML with a focus on bone marrow microenvironments.