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Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34⁺ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia.

ABSTRACT: Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34⁺ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34⁺ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8⁺ and FOXP3⁺ T cells and only single MUM1p⁺ B/plasma cells were detected in an area of ?10 ?m to CD34⁺ HSPC. Conclusions: CD8⁺ and FOXP3⁺ T cells are regularly seen in the 10 ?m area around CD34⁺ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34⁺ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.

SUBMITTER: Bauer M

PROVIDER: S-EPMC7825771 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34+ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia.

Bauer Marcus M Vaxevanis Christoforos C Al-Ali Haifa Kathrin HK Jaekel Nadja N Naumann Christin Le Hoa CLH Schaffrath Judith J Rau Achim A Seliger Barbara B Wickenhauser Claudia C

Cancers 20210107 2

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging ( ...[more]

PMID: 33430322

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Project description:BackgroundThe molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.MethodsWe enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.ResultsOf the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.ConclusionsPatients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).

Dataset Information

Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34⁺ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia.

Publications

Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34<sup>+</sup> Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia.

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