What question did this study set out to answer?

Investigate the molecular mechanisms and functional consequences of bone marrow stroma-mediated S100A8 and S100A9 induction in acute myeloid leukemia cells.

April 7, 2022Blood AdvancesOpen Access

Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset

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Authors

MBMartin BöttcherUniversity Hospital Magdeburg KPKonstantinos PanagiotidisDublin City University HBHeiko BrunsFriedrich-Alexander-Universität Erlangen-Nürnberg

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Implication

Preclinical study reveals that bone marrow stroma promotes chemoresistant S100A8/A9-high subsets in acute myeloid leukemia via IL-6 signaling, suggesting targetable microenvironment dynamics.

Key Points

Investigate the molecular mechanisms and functional consequences of bone marrow stroma-mediated S100A8 and S100A9 induction in acute myeloid leukemia cells.
Assessed gene expression profiles and S100A8/A9 levels in primary acute myeloid leukemia (AML) patient blasts and AML cell lines cultured with bone marrow stromal cells.
Profiled the phenotype, free fatty acid utilization, and drug susceptibility of S100A8/A9high AML cells under chemotherapeutics and BCL2 inhibition.
Investigated cytokine drivers and downstream pathways using molecular inhibitors targeting interleukin-6 (IL-6), Jak/STAT3 signaling, and fatty acid uptake.
Bone marrow stromal cross talk induced contact-independent, reversible S100A8/A9 expression in AML cells, driven by stromal-derived IL-6 activating the Jak/STAT3 pathway.
S100A8/A9high blasts were enriched in patient bone marrow over peripheral blood and exhibited increased free fatty acid utilization, a mature myeloid phenotype, and drug resilience.
Targeting the IL-6-Jak/STAT3 signaling axis or fatty acid uptake effectively prevented S100A8/A9high cell generation and overcame treatment resistance.

Cite This Study

Böttcher et al. (2022) studied this question.

synapsesocial.com/papers/6a7564b8f2cd31a1fadc0b74 https://doi.org/10.1182/bloodadvances.2021005938

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Implication

Preclinical study reveals that bone marrow stroma promotes chemoresistant S100A8/A9-high subsets in acute myeloid leukemia via IL-6 signaling, suggesting targetable microenvironment dynamics.

Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset

Discussion

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Implication

Key Points

Cite This Study

Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset

Discussion

Member takes

Implication

Key Points

Cite This Study

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