Immunophenotypically defined stem cell subsets in paediatric AML are highly heterogeneous and demonstrate differences...

Area of Science:

• Hematology
• Pediatric Oncology
• Cancer Stem Cell Biology

Background:

• Leukaemic stem cells (LSCs) in adult acute myeloid leukaemia (AML) are distinguishable from healthy haematopoietic stem cells (HSCs) by immunophenotype.
• Immunophenotypic characteristics of stem cells in pediatric AML remain less understood.

Purpose of the Study:

• To investigate the immunophenotypic differences of stem cells in pediatric AML.
• To identify aberrant surface markers and BCL-2 expression in pediatric AML stem cells.
• To compare findings with adult AML studies.

Main Methods:

• A 15-colour flow cytometry assay was used to analyze CD34+ CD38- bone marrow stem cells from 38 pediatric AML patients and 7 controls.
• Expression of eight aberrant surface markers and BCL-2 was assessed.
• Genetic analyses were performed on sorted stem cell subsets for clonality investigation.

Main Results:

• Fifty aberrant marker-positive (non-HSC-like) subsets with 41 distinct immunophenotypic profiles were identified.
• CD123, CLEC12A, and IL1RAP were the most frequently expressed aberrant markers.
• BCL-2 overexpression was observed specifically in immunophenotypically abnormal non-HSC-like subsets, with differential expression across cytogenetic subgroups.

Conclusions:

• Pediatric AML stem cell populations exhibit significant immunophenotypic heterogeneity.
• Certain aberrant markers effective in adult AML are not suitable for detecting leukemia-representing stem cells in pediatric patients.
• Findings suggest caution when extrapolating conclusions from adult AML studies to pediatric cases.