TY - JOUR
T1 - Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis
AU - Le, Phuong M.
AU - Andreeff, Michael
AU - Lokesh Battula, Venkata
N1 - Funding Information:
This work is supported by the Leukemia SPORE career development award (CA100632), Rolanette and Berdon Lawrence Research Award from Bone Disease Program of Texas, Institutional Research Grant (IRG) from MD Anderson Cancer Center, Cure Sonia Foundation and Golfers Against Cancer Foundation to VLB. In addition, this work was supported by grants from the National Institutes of Health (CA055164) and the MD Anderson Cancer Center Support Grant (CA016672), Cancer Prevention Research Institute of Texas (CPRIT, RP121010), and the Paul and Mary Haas Chair in Genetics to MA. We thank Dr. Marina Konopleva for her valuable suggestions in the preparation of this review article.
Publisher Copyright:
© 2018 Ferrata Storti Foundation.
PY - 2018/11/30
Y1 - 2018/11/30
N2 - The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic, and eventually to leukemic, cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models. The osteogenic niche, which consists of osteoprogenitors, preosteoblasts, mature osteoblasts, osteocytes and osteoclasts, has been shown to play a critical role in the maintenance and expansion of hematopoietic stem and progenitor cells as well as in their oncogenic transformation into leukemia stem/initiating cells. We have recently shown that acute myeloid leukemia cells induce osteogenic differentiation in mesenchymal stromal cells to gain a growth advantage. In this review, we discuss the role of the osteogenic niche in the maintenance of hematopoietic stem and progenitor cells, as well as in their transformation into leukemia cells. We also discuss the signaling pathways that regulate osteogenic nichehematopoietic stem and progenitor cells or osteogenic niche-leukemic stem/initiating cell interactions in the bone marrow, together with novel approaches for therapeutically targeting these interactions.
AB - The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic, and eventually to leukemic, cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models. The osteogenic niche, which consists of osteoprogenitors, preosteoblasts, mature osteoblasts, osteocytes and osteoclasts, has been shown to play a critical role in the maintenance and expansion of hematopoietic stem and progenitor cells as well as in their oncogenic transformation into leukemia stem/initiating cells. We have recently shown that acute myeloid leukemia cells induce osteogenic differentiation in mesenchymal stromal cells to gain a growth advantage. In this review, we discuss the role of the osteogenic niche in the maintenance of hematopoietic stem and progenitor cells, as well as in their transformation into leukemia cells. We also discuss the signaling pathways that regulate osteogenic nichehematopoietic stem and progenitor cells or osteogenic niche-leukemic stem/initiating cell interactions in the bone marrow, together with novel approaches for therapeutically targeting these interactions.
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U2 - 10.3324/haematol.2018.197004
DO - 10.3324/haematol.2018.197004
M3 - Review article
C2 - 30337364
AN - SCOPUS:85060873751
SN - 0390-6078
VL - 103
SP - 1945
EP - 1955
JO - Haematologica
JF - Haematologica
IS - 12
ER -