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The mechanisms of pathological extramedullary hematopoiesis in diseases

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Abstract

Extramedullary hematopoiesis (EMH) is the expansion and differentiation of hematopoietic stem and progenitor cells outside of the bone marrow. In postnatal life, as a compensatory mechanism for ineffective hematopoiesis of the bone marrow, pathological EMH is triggered by hematopoietic disorders, insufficient hematopoietic compensation, and other pathological stress conditions, such as infection, advanced tumors, anemia, and metabolic stress. Pathological EMH has been reported in many organs, and the sites of pathological EMH may be related to reactivation of the embryonic hematopoietic structure in these organs. As a double-edged sword (blood and immune cell supplementation as well as clinical complications), pathological EMH has been widely studied in recent years. In particular, pathological EMH induced by late-stage tumors contributes to tumor immunosuppression. Thus, a deeper understanding of the mechanism of pathological EMH may be conducive to the development of therapies against the pathological processes that induce EMH. This article reviews the recent progress of research on the cellular and molecular mechanisms of pathological EMH in specific diseases.

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Abbreviations

27HC:

27-Hydroxycholesterol

AML:

Acute myeloid leukemia

ASXL:

ASXL transcriptional regulator 2

CLP:

Common lymphoid progenitor

CMP:

Common myeloid progenitor

CMRPs:

Common myeloid repopulating progenitors

EIs:

Erythroblastic islands

EPCs:

Erythroid progenitor cells

EPO:

Erythropoietin

ERα:

Estrogen receptor α

G-CSF:

Granulocyte-colony stimulating factor

GM-CSF:

Granulocyte–macrophage colony stimulating factor

GMP:

Granulocyte–macrophage progenitor

HCC:

Hepatocellular carcinoma

HCMV:

Human cytomegalovirus

HPCs:

Hematopoietic progenitor cells

HSCs:

Hematopoietic stem cells

HSPCs:

Hematopoietic stem and progenitor cells

IFN-γ:

Interferon-γ

JAK2:

Janus kinase-2

LDL:

Low density lipoprotein

LepR:

Leptin receptor

MCMV:

Murine cytomegalovirus

M-CSF:

Macrophage-colony stimulating factor

MDSCs:

Myeloid-derived suppressor cells

MEP:

Megakaryocyte–erythrocyte progenitor

MERPs:

Megakaryocyte–erythrocyte repopulating progenitors

MkRPs:

Megakaryocyte repopulating progenitors

MRI:

Magnetic resonance imaging

MyRP:

Myeloid-restricted repopulating progenitor

NK:

Natural killer

PAMPs:

Pathogen-associated molecular patterns

Rheb1:

Ras homolog enriched in brain 1

ROS:

Reactive oxygen species

Setd1b:

SET domain containing 1B, histone lysine methyltransferase

Srebp2:

Sterol regulatory element binding transcription factor 2

TLRs:

Toll-like receptors

Treg:

Regulatory T

VCAM-1:

Vascular cell adhesion molecule-1

VLA-4:

Very late antigen-4

Zeb2:

Zinc finger E-box binding homeobox 2

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (Grant Nos. 81925030, 81972699, 81620108023 and 81472648).

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  1. Xinxin Yang and Degao Chen have contributed equally to this work.

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  1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Xinxin Yang, Degao Chen, Haixia Long & Bo Zhu

  2. Chongqing Key Laboratory of Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Bo Zhu

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Yang, X., Chen, D., Long, H. et al. The mechanisms of pathological extramedullary hematopoiesis in diseases. Cell. Mol. Life Sci. 77, 2723–2738 (2020). https://doi.org/10.1007/s00018-020-03450-w

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