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Solimando et al. J Cancer Metastasis Treat 2022;8:9 Journal of Cancer
DOI: 10.20517/2394-4722.2021.166
Metastasis and Treatment

Review Open Access

The bone marrow niche landscape: a journey
through aging, extrinsic and intrinsic stressors in

the haemopoietic milieu

Antonio Giovanni Solimando, Assunta Melaccio, Angelo Vacca, Roberto Ria
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari
Medical School, Bari 70124 Italy.

Correspondence to: Prof. Roberto Ria. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine
and Clinical Oncology, University of Bari Medical School, Policlinico - Piazza Giulio Cesare, Bari 11 I-70124, Italy.
E-mail: roberto.ria@uniba.it
How to cite this article: Solimando AG, Melaccio A, Vacca A, Ria R. The bone marrow niche landscape: a journey through aging,
extrinsic and intrinsic stressors in the haemopoietic milieu. J Cancer Metastasis Treat 2022;8:9.
https://dx.doi.org/10.20517/2394-4722.2021.166

Received: 24 Aug 2021 First Decision: 10 Dec 2021 Revised: 13 Jan 2022 Accepted: 24 Feb 2022 Published: 18 Mar 2022

Academic Editors: Lucio Miele, Gopal C. Kundu, Dominique A. Bonnet Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Inflammation and its effects in the bone marrow microenvironment represent a paradigmatic condition in which
the hematopoietic niche and the immune systems, thought to properly sustain blood cell production and
distinguish between friend and foe, can actively sustain a corrupted neighborhood within a chronic aberrant
inflamed state. The bone marrow niche hijacks the physiologic hematopoiesis. The interactions between the
hematopoietic stem cells and the niche in the bone marrow are critical determinants of quiescence. We examined
several approaches to confront the available evidence; three key points emerged, pointing to the chronic
inflammation process, especially the chronic infection and systemic inflammatory states, as leading causes of
hematopoietic stem cell depletion. Clonal hematopoiesis, defined as a relative expansion of individual clones, is
caused by somatic alterations in essential hematopoietic genes, which increase stem cell fitness. Moreover,
terminal differentiation plays a significant role in progenitor loss and inflammatory signaling, promoting clonal
selection and clonal hematopoiesis conditions. Specific myeloid malignancies as paradigmatic examples are
discussed as a condition associated with inflammation, including the 5q- syndrome, Philadelphia negative
myeloproliferative neoplasms, and chronic myeloid leukemia. Aging with increased fitness and hematopoietic stem
cell attrition, extrinsic stress, enhanced stressor-specific fitness, and intrinsic defect across the hematopoietic
process represent the route for novel insights in defective hematopoiesis. The discussion in this review also points

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
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