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Updated: Mar 8, 2026
Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes
Matheus Rodrigues Lopes1, João Kleber Novais Pereira1, Paula de Melo Campos1
1Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
Abstract:
The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1β, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.
Insights
Mesenchymal stromal cells (MSC) in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) impact T-cell proliferation. De novo AML MSC show increased IL-32, potentially driving chemoresistance by altering the bone marrow microenvironment.
Area of Science:
- Hematology
- Immunology
- Cancer Biology
Background:
- The bone marrow microenvironment influences leukemia cell survival and chemoresistance in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
- Mesenchymal stromal cells (MSC) are key components of this microenvironment, modulating immune responses and cellular interactions.
Purpose of the Study:
- To characterize cytokine expression and functional changes in MSC from patients with MDS, AML with myelodysplasia-related changes (MRC), and de novo AML.
- To investigate the role of specific cytokines, particularly IL-32, in regulating MSC function and leukemia cell interactions.
Main Methods:
- Comparative analysis of cytokine expression profiles in MSC derived from MDS, AML-MRC, and de novo AML patients.
- Functional assays assessing MSC effects on T lymphocyte proliferation.
- Evaluation of IL-32's role in stromal cell proliferation, chemotaxis, and crosstalk with leukemia cells.
Main Results:
- MDS-MSC significantly inhibited T-lymphocyte proliferation; AML-MSC showed inhibition only at low ratios.
- AML-MRC-derived MSC exhibited increased IL-6 expression compared to controls.
- De novo AML MSC showed increased expression of VEGFA, CXCL12, RPGE2, IDO, IL-1β, IL-6, and IL-32, with decreased IL-10.
Conclusions:
- Differences in MSC function and cytokine profiles exist between AML subtypes (AML-MRC vs. de novo AML), extending to the leukemic stem cell niche.
- IL-32 plays a significant role in regulating stromal cell proliferation, chemotaxis, and leukemia cell crosstalk, potentially contributing to chemoresistance.
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