Vashendriya V. V. Hira (Author), Cornelis J. F. van Noorden (Author), Hetty E. Carraway (Author), Jaroslaw P. Maciejewski (Author), Remco J. Molenaar (Author)

Abstract

Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes. Thus far, three types of HSC niches are recognized: endosteal, reticular and perivascular niches. However, we argue here that there is only one type of HSC niche, which consists of a periarteriolar compartment and a perisinusoidal compartment. In the periarteriolar compartment, hypoxia and low levels of reactive oxygen species preserve the HSC pool. In the perisinusoidal compartment, hypoxia in combination with higher levels of reactive oxygen species enables proliferation of progenitor cells and their mobilization into the circulation. Because HSC niches offer protection to LSCs against chemotherapy, we review novel therapeutic strategies to inhibit homing of LSCs in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, we list clinical trials of therapies that tackle LSCs in HSC niches to circumvent their protection against chemotherapy.

Keywords

medicinske znanosti;levkemija;zdravljenje;terapevtske strategije;hematopoietic stem cell niche;hijacking;leukemic stem cells;bone marrow;therapy resistance;leukemia;

Data

Language: English
Year of publishing:
Typology: 1.02 - Review Article
Organization: NIB - National Institute of Biology
UDC: 61
COBISS: 40483077 Link will open in a new window
ISSN: 0304-419X
Views: 23
Downloads: 8
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Other data

Secondary language: Slovenian
Secondary keywords: medicinske znanosti;levkemija;zdravljenje;terapevtske strategije;
Pages: str. 183-198
Volume: ǂVol. ǂ1868
Issue: ǂiss. ǂ1
Chronology: Aug. 2017
DOI: 10.1016/j.bbcan.2017.03.010
ID: 24669896