Spatial analysis reveals distinct immune phenotypes and ectopic lymphoid structures in pediatric acute myeloid leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB60363 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Because of the low mutational burden, children with acute myeloid leukemia (AML) are thought to have a ‘cold’ tumor microenvironment and consequently, a low likelihood of response to T cell-directed immunotherapies. Here, we provide a multidimensional overview of the tumor immune microenvironment in newly diagnosed pediatric AML. On a cohort level, we demonstrate wide variation in T cell infiltration with nearly one-third of cases harboring an immune-infiltrated bone marrow. These immune-infiltrated cases are characterized by a decreased abundance of M2-like macrophages, which we find to be associated with response to T cell-directed immunotherapy in adult AML. On an organizational level, we reveal the composition of spatially organized immune aggregates in pediatric AML, and show that in the adult setting such aggregates in post-treatment bone marrow and extramedullary sites associate with response to ipilimumab-based therapy. Altogether, our study provides immune correlates of response to T cell-directed immunotherapies and indicates starting points for further investigations into immunomodulatory mechanisms in AML.
2024-08-27 | GSE248597 | GEO
Project description:Comparison of immune-infiltrated bone marrow samples (n=6) with immune-depleted bone marrow samples (n=17) of pediatric acute myeloid leukemia patients using the Nanostring PanCancer IO 360 panel.
2024-08-27 | GSE228481 | GEO
Project description:This series represents leukemic samples obtained from pediatric AML patients at diagnosis and control normal bone marrow samples.
2007-08-25 | E-GEOD-2191 | biostudies-arrayexpress
Project description:In contrast to patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL), patients with acute myeloid leukemia (AML) have not yet benefited from recent advances in targeted immunotherapy. Repurposing immunotherapies that have been successfully used to target other hematological malignancies could, in case of a shared target antigen, represent a promising opportunity to expand the immunotherapeutic options for AML. Here, we evaluated the expression of CD19 in a large pediatric AML cohort, assessed the ex vivo AML killing efficacy of CD19-directed immunotherapies, and characterized the bone marrow immune microenvironment in pediatric AML, BCP-ALL, and non-leukemic controls. Out of 167 newly diagnosed de novo pediatric AML patients, 18 patients (11%) had CD19+ AML, with 61% carrying the translocation t(8;21)(q22;q22). Among CD19+ samples, we observed a continuum of CD19 expression levels on AML cells. In individuals exhibiting unimodal and high CD19 expression, the antigen was consistently present on nearly all CD34+CD38- and CD34+CD38+ subpopulations. In ex vivo AML-T cell co-cultures, blinatumomab demonstrated substantial AML killing, with an efficacy similar to BCP-ALL. In addition, CAR T cells could effectively eliminate CD19+ AML cells ex vivo. Furthermore, our immunogenomic assessment of the bone marrow immune microenvironment of newly diagnosed pediatric t(8;21) AML revealed that T- and NK cells had a less exhausted and senescent phenotype in comparison to pediatric BCP-ALL. Altogether, our study underscores the promise of CD19-directed immunotherapies for the treatment of pediatric CD19+ AML.
2024-08-08 | GSE270185 | GEO
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML This study characterizes CNA and LOH, gene expression and gene sequence mutations in a representative cross-section through subtypes of pediatric AML. Keywords: Affymetrix arrays were performed according to the maufacturers directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to DNA extraction 111 pediatric AML samples were studied using the Affymetrix U133A array.
2010-01-03 | E-GEOD-14471 | biostudies-arrayexpress
Project description:Pediatric acute myeloid leukemia (AML) is a heterogeneous disease with respect to biology as well as outcome. In this study, we investigated whether known biological subgroups of pediatric AML are reflected by a common microRNA (miRNA) expression pattern. We assayed 665 miRNAs in 165 pediatric AML samples. First, unsupervised clustering was performed to identify patient clusters with common miRNA expression profiles. Our analysis unraveled 14 clusters, seven of which had a known (cyto-)genetic denominator. Finally, a robust classifier was constructed to discriminate six known molecular aberration groups: 11q23-rearrangements, t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q21;q22), NPM1 and CEBPA mutations. The classifier achieved accuracies of 89%, 95%, 95%, 98%, 91% and 96%, respectively. Although lower sensitivities were obtained for the NPM1 and CEBPA (32% and 66%), relatively high sensitivities (84%-94%) were attained for the rest. Specificity was high in all groups (87%-100%). Due to a robust double-loop cross validation procedure we employed, the classifier only used expression of 47 miRNAs to generate the aforementioned accuracies. To validate the 47 miRNA signatures, we applied them to a publicly available adult AML dataset. Despite partial overlap of miRNA platforms and known molecular differences between pediatric and adult AML, the signatures performed reasonably well. This corroborates our claim that the reported miRNA signatures are not dominated by sample size bias in the pediatric AML dataset. We conclude that cytogenetic subtypes of pediatric AML have distinct miRNA expression patterns. Note that, reproducibility of the miRNA signatures in adult dataset suggests that the respective aberrations have a similar biology both in pediatric and adult AML
2017-04-01 | GSE94066 | GEO
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental file 'GSE15732_AML_175_SNP_Xba_signal.txt' contains the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15732 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental file 'GSE15714_AML_175_SNP_Hind_signal.txt' contains the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15714 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental files 'GSE15730_AML_175_SNP_Nsp_signal.txt' and 'GSE15730_AML_176_SNP_Nsp_signal.txt' contain the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-04-13 | E-GEOD-15730 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental files 'GSE15731_AML_175_SNP_Sty_signal.txt' and 'GSE15731_AML_176_SNP_Sty_signal.txt' contain the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15731 | biostudies-arrayexpress