Characterization of myelodysplastic syndromes hematopoietic stem and progenitor cells using mass cytometry

• Published in: Cytometry. Part B, Clinical cytometry Clinical cytometry, 2023-03, Vol.104 (2), p.128-140
• Main Authors: Bachas, Costa, Duetz, Carolien, Spronsen, Margot F., Verhoeff, Jan, Garcia Vallejo, Juan J., Jansen, Joop H., Cloos, Jacqueline, Westers, Theresia M., Loosdrecht, Arjan A.
• Format: Article
• Language: English
• Subjects: Abnormalities; Acute myeloid leukemia; Bone marrow; CD34 antigen; CD44 antigen; Clusters; Computer applications; Cytometry; Data analysis; Disorders; Flow Cytometry; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Humans; Leukemia; Leukemia, Myeloid, Acute - genetics; leukemic transformation; mass cytometry; Myelodysplastic syndrome; myelodysplastic syndromes; Myelodysplastic Syndromes - metabolism; Phenotypes; Populations; Progenitor cells; Risk; Risk Factors; Stem cells
• ISSN: 1552-4949; 1552-4957
• DOI: 10.1002/cyto.b.22066

Background Myelodysplastic syndromes (MDS) at risk of transformation to acute myeloid leukemia (AML) are difficult to identify. The bone marrows of MDS patients harbor specific hematopoietic stem and progenitor cell (HSPC) abnormalities that may be associated with sub‐types and risk‐groups. Leukemia‐associated characteristics of such cells may identify MDS patients at risk of progression to AML and provide insight in the pathobiology of MDS. Methods Bone marrow samples from healthy donors (n = 10), low risk (n = 12) and high risk (n = 13) MDS patients were collected, in addition, AML samples for 5 out of 6 MDS patients that progressed. Mass cytometry was applied to assess expression of stem cell subset and leukemia‐associated immunophenotype markers. Results We analyzed the data using FlowSOM to cluster cells with similar expression of 10 commonly used stem cell markers. Metaclusters (n = 20) of these clusters represented populations of cells with a related phenotype, largely resembling known stem cell subsets. Within specific subsets, intra‐cellular expression levels of pCREB, IkBα, or pS6 differed significantly between healthy bone marrow (HBM) and MDS or consecutive secondary AML samples. CD34, CD44, and CD49f expression was significantly increased in high risk MDS and AML‐associated metaclusters. We identified MDS/sAML cells with aberrant phenotypes when compared to HBM. Such cells were observed in clusters of both primary MDS and secondary AML samples. Conclusions High‐dimensional mass cytometry and computational data analyses enabled characterization of HSPC subsets in MDS and identification of leukemia stem cell populations based on their immunophenotype. Stem cells in MDS that display leukemia‐associated features may predict the risk of developing AML.