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Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
Version 1
: Received: 10 September 2020 / Approved: 13 September 2020 / Online: 13 September 2020 (11:51:13 CEST)
How to cite:
Bauer, M.; Vaxevanis, C.; Al-Ali, H.K.; Jaekel, N.; Naumann, C.L.H.; Schaffrath, J.; Rau, A.; Seliger, B.; Wickenhauser, C. Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia. Preprints2020, 2020090280. https://doi.org/10.20944/preprints202009.0280.v1
Bauer, M.; Vaxevanis, C.; Al-Ali, H.K.; Jaekel, N.; Naumann, C.L.H.; Schaffrath, J.; Rau, A.; Seliger, B.; Wickenhauser, C. Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia. Preprints 2020, 2020090280. https://doi.org/10.20944/preprints202009.0280.v1
Bauer, M.; Vaxevanis, C.; Al-Ali, H.K.; Jaekel, N.; Naumann, C.L.H.; Schaffrath, J.; Rau, A.; Seliger, B.; Wickenhauser, C. Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia. Preprints2020, 2020090280. https://doi.org/10.20944/preprints202009.0280.v1
APA Style
Bauer, M., Vaxevanis, C., Al-Ali, H.K., Jaekel, N., Naumann, C.L.H., Schaffrath, J., Rau, A., Seliger, B., & Wickenhauser, C. (2020). Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia. Preprints. https://doi.org/10.20944/preprints202009.0280.v1
Chicago/Turabian Style
Bauer, M., Barbara Seliger and Claudia Wickenhauser. 2020 "Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia" Preprints. https://doi.org/10.20944/preprints202009.0280.v1
Abstract
Purpose: Myelodysplastic syndromes (MDS) are caused by a stem cell failure, but the relationship between immune dysregulation and the course of disease has not yet been analyzed in detail. Experimental design: To get insights into the pathophysiologic and clinical relevance of the histotopography of immune cell subpopulations in this process, the immune cell infiltrate with focus on its spatial distribution was determined by multispectral imaging (MSI) in 147 bone marrow biopsies from MDS or secondary acute myeloid leukemia (sAML) patients and healthy controls (HC). In addition, the data were correlated to genetic alterations and clinical features of these patients including therapy response. Results: A high inter-tumoral heterogeneity in the frequency and spatial distribution of CD3+CD8+, CD3+CD8-, CD3+FOXP3+ T cell subsets, MUM1p+CD3- post-germinal B/plasma cells and CD34+ blasts was found in MDS and sAML samples. In HC only few B cells/plasma cells, but no T cell subpopulations were detected in the proximity to CD34+ blasts. In contrast, the frequency of these lymphocytes was increased in proximity to CD34+ blasts in both MDS and sAML independent of the karyotype, genetic alterations frequently detected in MDS, clinical risk stratification systems or treatment response to hypomethylating agents. Furthermore, an increased frequency of CD3+CD8+ T cells and MUM1p+ CD3- B cells was found in responders to epigenetic drugs. Conclusions: Thus, we conclude that (i) T cell subsets do not belong to the normal stem cell niche, (ii) the presence of T and B cell subpopulations not directly affect the course of MDS, (iii) lymphocytes in the proximity to CD34+ blasts might indicate defective stem cell properties and (iv) the number of lymphocytes is a predictor of therapy response to hypomethylating agents.
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
