SLPI overexpression in hMSCs could be implicated in the HSC gene expression profile in AML

Area of Science:

• Hematology
• Cancer Biology
• Stem Cell Biology

Background:

• Acute myeloid leukemia (AML) arises from hematopoietic stem cells (HSCs) transforming into leukaemic stem cells (LSCs).
• The bone marrow (BM) microenvironment, including mesenchymal stromal cells (hMSCs), is critical for HSC maintenance.
• Alterations in hMSCs within the BM niche may influence HSC behavior in AML.

Purpose of the Study:

• To investigate if the secretome of hMSCs from AML patients (hMSC-AML) affects HSC gene expression.
• To identify specific proteins in the hMSC-AML secretome that may impact HSCs.
• To explore the functional consequences of these secretome alterations on HSCs.

Main Methods:

• Proteomic analysis of secretomes from cocultures of hMSC-AML and healthy donor HSCs (hMSC-HD).
• Measurement of secretory leukocyte protease inhibitor (SLPI) levels in hMSC secretomes and BM plasma from AML patients.
• Transcriptome analysis of HSCs following coculture with hMSC-AML versus hMSC-HD.

Main Results:

• The secretome of hMSC-AML cocultured with healthy HSCs showed increased SLPI levels compared to hMSC-HD.
• Elevated SLPI expression was also detected in the BM plasma of AML patients.
• HSCs cocultured with hMSC-AML exhibited altered expression of genes related to cell cycle, proliferation, and apoptosis, including changes in CCNA2, CCNE2, CDK1, and CDKN2A.

Conclusions:

• The altered secretome of hMSC-AML, particularly elevated SLPI, can modify HSC gene expression.
• These changes in HSCs may involve key molecular mechanisms relevant to AML development and progression.
• SLPI emerges as a potential factor contributing to the dysregulation of the HSC niche in AML.