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Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome
Alexander Sternberg1, Sally Killick, Tim Littlewood
1Department of Hematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom OX3 9DU.
Abstract:
Early, low-risk International Prognostic Scoring System (IPSS) myelodysplastic syndrome (MDS) is a heterogeneous disorder where the molecular and cellular hematopoietic defects are poorly understood. To gain insight into this condition, we analyzed gene expression profiles of marrow CD34+ progenitor cells from normal-karyotype, low-blast-count MDS patients, age-matched controls, and patients with non-MDS anemia. Given the heterogeneity of early MDS, a surprisingly consistent finding was decreased expression of B-cell lineage-affiliated genes in MDS patients compared with healthy controls and 3 of 5 samples with non-MDS anemia. Both patients with non-MDS anemia with reduced B-cell gene expression were on chemotherapy. In 25 of 27 of the original samples and 9 further MDS samples, Taqman real-time polymerase chain reaction (PCR) confirmed these data. Flow cytometry on unfractionated marrow from independent samples also demonstrated reduced B-cell progenitors in MDS patients compared with healthy controls. These novel findings suggest a common perturbation in early MDS hematopoiesis. They also provide the rationale for a larger study to evaluate the diagnostic utility of reduced B-cell progenitor number as a diagnostic biomarker of early low-risk MDS, which can pose a diagnostic challenge.
Insights
Early myelodysplastic syndromes (MDS) show reduced B-cell gene expression and fewer B-cell progenitors. This finding suggests a common hematopoietic defect and may offer a diagnostic biomarker for low-risk MDS.
Area of Science:
- Hematology
- Molecular Biology
- Immunology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- Early, low-risk MDS is heterogeneous with poorly understood molecular and cellular defects.
- Accurate diagnosis of early MDS can be challenging.
Purpose of the Study:
- To investigate gene expression profiles in CD34+ progenitor cells from MDS patients.
- To identify molecular and cellular defects in early, low-risk MDS.
- To explore the diagnostic utility of B-cell lineage gene expression and progenitor numbers.
Main Methods:
- Analysis of gene expression profiles in marrow CD34+ progenitor cells.
- Comparison between MDS patients, healthy controls, and non-MDS anemia patients.
- Validation using Taqman real-time polymerase chain reaction (PCR).
- Assessment of B-cell progenitors via flow cytometry.
Main Results:
- MDS patients consistently showed decreased expression of B-cell lineage-affiliated genes.
- Reduced B-cell gene expression was observed in MDS compared to healthy controls.
- Flow cytometry confirmed a reduced number of B-cell progenitors in MDS patients.
- Chemotherapy in non-MDS anemia patients was associated with reduced B-cell gene expression in some cases.
Conclusions:
- A common perturbation in early MDS hematopoiesis involves reduced B-cell lineage affiliation.
- Reduced B-cell progenitor numbers may serve as a diagnostic biomarker for early low-risk MDS.
- Further studies are warranted to evaluate the diagnostic utility of this finding.
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