Normal and leukemic stem cell niches: insights and therapeutic opportunities.
Hematopoietic stem cells (HSCs) rely on instructive cues from the bone marrow (BM) niche to maintain their quiescence and adapt blood production to the organism's needs. Alterations in the BM niche are commonly observed in blood malignancies and directly contribute to the aberrant function of disease-initiating leukemic stem cells (LSCs). Here, we review recent insights into the cellular and molecular determinants of the normal HSC niche and describe how genetic changes in stromal cells and leukemia-induced BM niche remodeling contribute to blood malignancies. Moreover, we discuss how these findings can be applied to non-cell-autonomous therapies targeting the LSC niche.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Department of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Koen
K
Schepers
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Timothy B
TB
Campbell
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: passeguee@stemcell.ucsf.edu.
Emmanuelle
E
Passegué
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment