Gene Expression Profiles with Common Translocations in Acute Myeloid Leukemia (AML) using SAGE
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3255 | GEO | 2005/12/01
SECONDARY ACCESSION(S): PRJNA92907
REPOSITORIES: GEO
Similar Datasets
Project description:SAGE was used to profile gene expression in leukemic myeloid progenitor cells of AML patients with t(8;21), t(15;17), t(9;11) and inv(16). Keywords: SAGE analysis of gene expression in leukemic myeloid progenitor cells isolated from bone marrow Bone marrow cells from 4 patients with de novo t(9;11), 3 with treatment-related t(9;11), and 5 each with inv(16), t(15;17), t(8;21) were used for the study. Each sample contained at least 75% affected cells with no other chromosome abnormalities at cytogenetic level. Mononuclear cells were purified from bone marrow cells for each sample, and CD15+ myeloid progenitor cells were isolated from these mononuclear cells. Poly A+ RNA were isolated from CD15+ myeloid progenitor cells of each sample for SAGE tag collection.
2005-11-30 | E-GEOD-3255 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21) (n=21), inv(16) (n=17) or MLL-rearrangement (n=35) by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases, which also included 12 t(15;17) and 5 t(7;12) samples.
2014-01-01 | E-GEOD-52541 | biostudies-arrayexpress
Project description:Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion. Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set).
2011-12-24 | E-GEOD-34714 | biostudies-arrayexpress
Project description:Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion. Training set.
2011-12-21 | E-GEOD-34577 | biostudies-arrayexpress
Project description:Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
2011-12-24 | GSE34714 | GEO
Project description:Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
2011-12-21 | GSE34577 | GEO
Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner.
2014-01-01 | GSE52541 | GEO
Project description:T(8;21), which produces the AML1-ETO (AE) fusion oncoprotein, is one of the most common chromosomal abnormalities in AML patients. Despite its prevalence among patients, it has remained challenging to study the impact of AE on leukemia development in vivo due to limitations of the current t(8;21) mouse models. Here, we devised a germline transmitted transgenic Rosa26-AE9a knock-in mouse model that expresses AE9a protein, a truncated AE variant, at moderately elevated levels compared to endogenous RUNX1. These mice develop myeloid leukemia with longer latency and lower penetrance compared to mice using the AE9a retroviral transduction-transplantation model. Pre-leukemic mice exhibited myeloid progenitor skewing in their bone marrow, with more granulocyte-monocyte progenitors (GMP) at the expense of megakaryocyte-erythroid progenitors (MEP). Importantly, hematopoietic stem and progenitor cells (HSPCs) of pre-leukemic mice had increased clonogenic potential. We performed single cell RNA-sequencing on pre-leukemic HSPCs and confirmed both this granulocytic bias and hindered differentiation. Overall, we have overcome the limitation of uncontrolled AE9a oncogene expression in the retroviral transduction-transplantation mouse model and have devised a new germline transmitted Rosa26 locus AE9a knock-in model that more faithfully represents t(8;21) human disease.
2023-10-11 | GSE173712 | GEO
Project description:Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biological and clinical heterogeneity within these cytogenetic groups, which is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n=93) of AML patients with CBF leukemia [inv(16) n=55, t(8;21) n=38]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n=35) characterized by shorter overall survival times (P=0.03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21)-subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P=0.011 and P=0.026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the ?favorable? CBF leukemias anti-apoptotic mechanisms and deregulated mTOR-signaling, and in the newly defined ?unfavorable? subgroup aberrant MAPKinase-signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biological basis for the heterogeneity observed in CBF leukemia.
2007-06-10 | E-SMDB-4056 | biostudies-arrayexpress