João Antonio Ribeiro De Sousa

Brazil

The role of the bone marrow microenvironment in leukemia progression and therapeutic resistance

1. João Antonio Ribeiro de Sousa, UNINASSAU College, Petrolina, Brazil.

Abstract

Background

Leukemia is a type of hematologic cancer characterized by the abnormal proliferation of bone marrow progenitor cells. In recent years, the role of the bone marrow (BM) microenvironment has been widely recognized as a crucial factor in leukemia progression and the development of therapeutic resistance. The microenvironment is composed of a complex network of stromal cells, growth factors, cytokines, and extracellular matrix components that directly interact with leukemic cells, promoting their survival, proliferation, and evasion of programmed cell death (apoptosis). This microenvironment also facilitates resistance to chemotherapy and immunotherapy, making leukemia treatment a significant clinical challenge.

Methods

To conduct this literature review, a search was carried out in scientific databases such as PubMed, Scopus, and Google Scholar, using the keywords: “bone marrow microenvironment,” “leukemia progression,” “therapeutic resistance,” “stromal cells,” and “cytokines.” Studies published between 2015 and 2023 were included. Only peer-reviewed articles and relevant publications in high-impact scientific journals were considered. After an initial analysis of titles and abstracts, 40 articles were selected for full review, with an emphasis on the biological and therapeutic mechanisms associated with the interaction between the bone marrow microenvironment and leukemic cells.

Results

he reviewed studies indicate that the bone marrow microenvironment plays an essential role in leukemia progression through various molecular and cellular pathways. Bone marrow stromal cells, such as fibroblasts, endothelial cells, and mesenchymal cells, provide physical and biochemical support to leukemic cells, promoting their survival and protecting them from therapeutic agents.

Soluble factors secreted by the microenvironment, such as interleukins (IL-6, IL-8), chemokines (CXCL12), and growth factors (TGF-?, VEGF), have been associated with the activation of pro-survival signaling pathways, such as PI3K/AKT/mTOR and NF-?B, which contribute to treatment resistance. These interactions create a protective niche where leukemic cells can evade therapy-induced apoptosis and remain in a dormant or quiescent state, favoring disease relapse after periods of remission.

Conclusions

The bone marrow microenvironment plays a crucial role in leukemia progression and resistance to conventional treatments. The complex interactions between leukemic cells and the microenvironment create a protective niche that favors resistance to apoptosis and disease persistence, even after aggressive therapies. New therapeutic approaches aimed at disrupting these interactions or modulating the microenvironment components represent a promising strategy to overcome treatment resistance and improve clinical outcomes in leukemia patients.