Gene expression data from sorted primary human acute myeloid leukemia (AML) samples
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ABSTRACT:
PROVIDER: PRJNA524344 | ENA |
REPOSITORIES: ENA
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Project description:Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation. Analysis of gene expression in FACS sorted AML fractions that were functionally determined to be enriched for LSC or not (25 and 29 respectively).
2011-08-27 | E-GEOD-30375 | biostudies-arrayexpress
Project description:Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation.
2011-08-28 | GSE30375 | GEO
Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in two FLT3+ AML Pt samples.
2020-03-02 | PXD015639 | Pride
Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in two FLT3+ AML Pt samples and this data is deposited in PXD015639 . Here are the corresponding lysate samples
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Project description:In vivo studies indicate that human acute myeloid leukaemia (AML) originates from subpopulations of neoplastic cells with stem cell properties, thereby laying the foundation for the cancer stem cell concept. For clinically apparent disease to occur, cancer-initiating cells must also escape immune control. Here we show that stemness and immune evasion are closely intertwined in AML. Patients with AML harbour leukaemic subpopulations that lack expression of ligands for the danger detector NKG2D, a critical mediator of immune surveillance, which stimulates anti-tumour immunity by cytotoxic lymphocytes such as natural killer (NK) cells. We compared NKG2DLneg and NKG2DLpos subfractions from n=5 patients (each measured in triplicates) and found that NKG2DLneg cells displayed amongst others stemness characteristics.Our findings identify immune privilege as a general feature of LSCs, and provide a conceptual framework for the integration of two central hypotheses of cancer development – the concepts of cancer stem cells and immune escape
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Project description:Gene expression profiles of primary samples of acute myeloid leukemia (AML)
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Project description:A deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
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