Single cell transcriptomics derived combinatorial markers distinguished leukemic stem cells from hematopoietic stem...

Area of Science:

• Hematology
• Cancer Biology
• Immunology

Background:

• Leukemic stem cells (LSCs) drive relapse and chemoresistance in acute myeloid leukemia (AML).
• LSCs originate from hematopoietic stem cells (HSCs) with genetic/molecular aberrations.
• Phenotypic similarities between HSCs and LSCs, particularly in the CD34+CD38- fraction, challenge their differentiation and precise quantification.

Purpose of the Study:

• To identify novel cell surface markers for discriminating LSCs from HSCs using single-cell transcriptomics.
• To validate candidate markers for LSC identification in both CD34+ and CD34- AML patient populations.
• To assess the potential of combinatorial marker panels for LSC burden quantification and clinical utility.

Main Methods:

• Single-cell transcriptomic analysis of AML bone marrow samples.
• Identification and validation of differentially expressed cell surface markers between LSCs and HSCs.
• Expression analysis of candidate markers (CD48, CD52, CD96, CD88) in CD34+ and CD34- AML fractions.

Main Results:

• Several candidate markers, including CD48, CD52, CD96, and CD88, showed distinct expression patterns between LSCs and HSCs.
• CD52, CD96, and CD48 were significantly over-expressed in LSCs compared to HSCs.
• These markers are potential biomarkers for LSC identification in both CD34+ and CD34- AML.

Conclusions:

• An expanded combinatorial marker panel, including CD52, CD96, and CD48, can enhance LSC identification and differentiation from HSCs.
• These markers show promise for improved LSC quantification, measurable residual disease assessment, prognostication, and correlation with treatment outcomes in AML.
• Further evaluation in larger AML cohorts is warranted to confirm clinical utility.