Project description:Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3-ITD mutation, and to evaluate the utility of a FLT3 signature for prognostication. The dataset comprises gene-expression profiles of 137 normal karyotype acute myeloid leukemia (NK-AML) specimens carried out using Stanford cDNA microarrays, to accompany the study of L Bullinger et al. For each array, Channel 2 represents Cy5-labeled NK-AML RNA, and Channel 1 Cy3-labeled universal reference RNA. Keywords: Logical Set
Project description:Gene-expression profiling according to MN1 mRNA expression levels in de novo cytogenetically normal acute myeloid leukemia patients aged 60 years or older.
Project description:microRNA-expression profiling according to MN1 mRNA expression levels in de novo cytogenetically normal acute myeloid leukemia patients aged 60 years or older.
Project description:Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3-ITD mutation, and to evaluate the utility of a FLT3 signature for prognostication. The dataset comprises gene-expression profiles of 137 normal karyotype acute myeloid leukemia (NK-AML) specimens carried out using Stanford cDNA microarrays, to accompany the study of L Bullinger et al. For each array, Channel 2 represents Cy5-labeled NK-AML RNA, and Channel 1 Cy3-labeled universal reference RNA. Keywords: Logical Set DNA microarrays were used to profile gene expression in a training set of 65 NK-AML cases. Supervised analysis was applied to build a gene expression-based predictor of FLT3-ITD mutation status. The predictor was then evaluated by classifying expression profiles from an independent test set of 72 NK-AML cases.
Project description:Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of de novo CN-AML patients. Among 43 treatment response-related genes, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P<0.001) in ours and 3 other validation cohorts. In conclusion, we developed a simple mRNA expression signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients.
Project description:Gene-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia.
Project description:microRNA-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia patients <60 years.
Project description:MicroRNA-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia patients >=60 years.
Project description:Approximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of Nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal. These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor. 78 de novo AMLs, negative for AML-associated chromosomal translocations at the cytogenetic and/or molecular level.
Project description:The pretreatment karyotype of leukemic blasts is currently the key determinant in therapy decision-making in acute myeloid leukemia (AML). However, approximately fifty percent of AML patients, often carrying a normal karyotype, are currently unclassifiable based these established methods. Gene expression profiling has proven to be valuable for risk stratification of AML. This is a repository of 662 adult AML cases characterized on gene expression microarrays and used for different studies investigating the mechanisms underlying leukemogenesis. Bone marrow aspirates or peripheral blood samples of three independent representative cohorts of de novo AML patients, comprising 277, 256 and 129 cases respectively, were collected at diagnosis. Gene expression profiling was performed on 662 adult AML patients who have been treated according to Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON/SAKK) AML-04, -04A, -29, -32, -42, -42A, -43 and -92 protocols (available at http://www.hovon.nl). All patients provided written informed consent in accordance with the Declaration of Helsinki, and the study was approved by all participating institutional review boards. Blast cell purification and RNA isolation were performed as previously described (Valk et al., Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia, New England Journal of Medicine, 2004).
