Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes

Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and m...

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Bibliographic Details
Published in:PloS one 2018-05, Vol.13 (5), p.e0197823-e0197823
Main Authors: Ostendorf, Benjamin N, Flenner, Eva, Flörcken, Anne, Westermann, Jörg
Format: Article
Language:English
Subjects:
Aberration
Age
B-cell lymphoma
Biology and Life Sciences
Biomarkers
Biopsy
Bone marrow
Cancer
CD44 antigen
Chronic lymphocytic leukemia
Compartments
Development and progression
Diagnostic systems
Disorders
Flow cytometry
Genetic aspects
Health aspects
Hematology
Hematopoiesis
Hematopoietic stem cells
Immunology
Infiltration
Lectins
Leukemia
Lymphocytes B
Lymphoma
Malignancy
Medical research
Medicine and Health Sciences
Myelodysplastic syndrome
Myelodysplastic syndromes
Oncology
Patients
Phenotypes
Physiological aspects
Progenitor cells
Research and Analysis Methods
Stem cells
Surface markers
Therapeutic applications
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Summary:Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0197823