Hematopoietic versus leukemic stem cell quiescence: Challenges and therapeutic opportunities

O’Reilly, Eimear; Zeinabad, Hojjat Alizadeh; Szegezdi, Éva

doi:10.1016/j.blre.2021.100850

Cited by 53 publications

(52 citation statements)

References 269 publications

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“…LSCs can also be directly targeted based on their phenotypic and functional differences compared to healthy HSCs. These strategies are beyond the scope of this article and have been reviewed elsewhere (31,(138)(139)(140).…”

Section: How To Target the Leukemic Stem Cell Nichementioning

confidence: 99%

Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities

Marchand

Pinho

2021

Front. Immunol.

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Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. While complete remission can be obtained with intensive chemotherapy in young and fit patients, relapse is frequent and prognosis remains poor. Leukemic cells are thought to arise from a pool of leukemic stem cells (LSCs) which sit at the top of the hierarchy. Since their discovery, more than 30 years ago, LSCs have been a topic of intense research and their identification paved the way for cancer stem cell research. LSCs are defined by their ability to self-renew, to engraft into recipient mice and to give rise to leukemia. Compared to healthy hematopoietic stem cells (HSCs), LSCs display specific mutations, epigenetic modifications, and a specific metabolic profile. LSCs are usually considered resistant to chemotherapy and are therefore the drivers of relapse. Similar to their HSC counterpart, LSCs reside in a highly specialized microenvironment referred to as the “niche”. Bidirectional interactions between leukemic cells and the microenvironment favor leukemic progression at the expense of healthy hematopoiesis. Within the niche, LSCs are thought to be protected from genotoxic insults. Improvement in our understanding of LSC gene expression profile and phenotype has led to the development of prognosis signatures and the identification of potential therapeutic targets. In this review, we will discuss LSC biology in the context of their specific microenvironment and how a better understanding of LSC niche biology could pave the way for new therapies that target AML.

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Section: How To Target the Leukemic Stem Cell Nichementioning

confidence: 99%

Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities

Marchand

Pinho

2021

Front. Immunol.

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“…S4A †), attesting of the adequate standardization of this system. In addition, since some HSC have been described to become quiescent in their BM niche, 51 we validated that most CD45 + cells were Ki67 − or H3K27me3 + (ref. 47) (Fig.…”

Section: A Minimal Functional Bm-like Unit To Host and Sustain Normal Hematopoiesismentioning

confidence: 66%

A minimal standardized human bone marrow microphysiological system to assess resident cell behavior during normal and pathological processes

et al. 2022

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“…The LT/ST-HSCs reside in specialized niches that in the cavities of the trabecular regions in long bones. Multiple cellular types, soluble factors and components of the extracellular matrix form these niches [ 90 , 91 ]. The endosteal niche, located at the endosteal surface of the bone is characterized by bone regenerating osteoblasts (OBs) [ 92 ].…”

Section: Bm Niche Of Lt/st-hscs and Lscsmentioning

confidence: 99%

“…The endosteal niche, located at the endosteal surface of the bone is characterized by bone regenerating osteoblasts (OBs) [ 92 ]. The OB cells regulate LT-HSCs quiescence by producing CXC motif chemokine 12 ligand (CXCL12), transforming growth factor β (TGFβ) and angiopoitin-1 (ANG-1) [ 90 ]. The arteriolar niche is located aside vascular structures and brings LT/ST-HSCs in close proximity to endothelial cells (ECs) and mesenchymal stromal/stem cells (MSCs) [ 93 ].…”

Section: Bm Niche Of Lt/st-hscs and Lscsmentioning

confidence: 99%

Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells

Mayer

Hoelbl-Kovacic

Sexl

et al. 2022

Cancers

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Hematopoietic stem cells (HSCs) are rare, self-renewing cells that perch on top of the hematopoietic tree. The HSCs ensure the constant supply of mature blood cells in a tightly regulated process producing peripheral blood cells. Intense efforts are ongoing to optimize HSC engraftment as therapeutic strategy to treat patients suffering from hematopoietic diseases. Preclinical research paves the way by developing methods to maintain, manipulate and expand HSCs ex vivo to understand their regulation and molecular make-up. The generation of a sufficient number of transplantable HSCs is the Holy Grail for clinical therapy. Leukemia stem cells (LSCs) are characterized by their acquired stem cell characteristics and are responsible for disease initiation, progression, and relapse. We summarize efforts, that have been undertaken to increase the number of long-term (LT)-HSCs and to prevent differentiation towards committed progenitors in ex vivo culture. We provide an overview and compare methods currently available to isolate, maintain and enrich HSC subsets, progenitors and LSCs and discuss their individual advantages and drawbacks.

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Hematopoietic versus leukemic stem cell quiescence: Challenges and therapeutic opportunities

Cited by 53 publications

References 269 publications

Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities

Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities

A minimal standardized human bone marrow microphysiological system to assess resident cell behavior during normal and pathological processes

Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells

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