Concise Review: The Malignant Hematopoietic Stem Cell Niche. (23rd September 2016)

• Record Type: Journal Article
• Authors: Yao, Juo‐Chin; Link, Daniel C.
• Is Part Of: Stem cells. Volume 35:Number 1(2017:Jan.)
• Page Start: 3
• Page End: 8
• Publication Date: 2016-09-23
• Subjects: Hematologic malignancies -- Hematopoietic stem cells -- Bone marrow stromal cells -- Stem cell‐microenvironment interactions; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2487
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Hematopoietic stem cell (HSC) proliferation, self‐renewal, and trafficking are dependent, in part, upon signals generated by stromal cells in the bone marrow. Stromal cells are organized into niches that support specific subsets of hematopoietic progenitors. There is emerging evidence that malignant hematopoietic cells may generate signals that alter the number and/or function of specific stromal cell populations in the bone marrow. At least in some cases, the resulting alterations in the bone marrow microenvironment confer a competitive advantage to the malignant HSC and progenitor cells and/or render them less sensitive to chemotherapy. Targeting these signals represents a promising therapeutic strategy for selected hematopoietic malignancies. In this review, we focus on two questions. How do alterations in bone marrow stromal cells arise in hematopoietic malignancies, and how do they contribute to disease pathogenesis? Stem Cells 2017;35:3–8 Abstract : Paracrine loops involving malignant hematopoietic cells and stromal cells. A) In chronic myelogenous leukemia (CML), myeloid cells produce granulocyte colony‐stimulating factor (GCSF) (1) that acts on macrophages to suppress CXCL12 expression in stromal cells (e.g., CAR cells) (2), which in turn, leads to the mobilization of leukemic cells into the circulation (3). CML myeloid cells also may alter the bone marrow microenvironment through production of CCL3, thrombopoietin (not shown), and through direct stromal cell contact to induce the expansion of dysfunctional osteolineage cells (4). These altered osteolineage cells have decreased production of CXCL12 and other niche factors, which compromises their ability to support normal hematopoietic stem cells. B) B lymphoma cells produce fibroblast growth factor‐4 (FGF4) that signals through the fibroblast growth factor receptor‐1 (FGFR1) on endothelial cells to increase their expression of the Notch ligand, Jagged1 (1). This increase in endothelial Jagged1 then activates Notch2 on B lymphoma cells to induce their proliferation (2), completing the paracrine loop.