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GSE13693
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7R), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 288 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify new markers for minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL), we compared genome-wide gene expression of lymphoblasts from 270 patients with newly diagnosed childhood ALL to that of normal CD19 CD10 B-cell progenitors (n=4). Expression of 30 genes differentially expressed by > 3-fold in at least 25% of cases of ALL (or 40% of ALL subtypes) was tested by flow cytometry in 200 B-lineage ALL and 61 nonleukemic BM samples, including samples containing hematogones. Of the 30 markers, 22 (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially expressed in up to 81.4% of ALL cases; expression of some markers was associated with the presence of genetic abnormalities. Results of MRD detection by flow cytometry with these markers correlated well with those of molecular testing (52 follow-up samples from 18 patients); sequential studies during treatment and diagnosis-relapse comparisons documented their stability. When incorporated in 6-marker combinations, the new markers afforded the detection of 1 leukemic cell among 105 BM cells. These new markers should allow MRD studies in all B-lineage ALL patients, and substantially improve their sensitivity.
Publication Title
New markers for minimal residual disease detection in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Mixed-lineage leukemias represent about 3-5% of acute leukemias occurring in patients of all ages and comprise several different subtypes (biphenotypic, bilineal, and lineage switch). The optimal therapeutic approach to these cases, especially in pediatric patients, has not been defined. We used microarrays to detail the gene expression of pediatric patients with biophenotypic leukemia.
Publication Title
Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML
Publication Title
Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1492 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 357 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An International Multi-Center Study to Define the Clinical Utility of MicroarrayBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study)
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 204 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 175 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We studied a cohort of 221 high-risk pediatric B-progenitor ALL patients that excluded known high risk ALL subtypes (BCR-ABL1 and infant ALL), using Affymetrix single nucleotide polymorphism microarrays, gene expression profiling and candidate gene resequencing. A CNA poor outcome predictor was identified using a semi-supervised principal components approach, and tested in an independent validation cohort of 258 pediatric B-progenitor ALL cases. Over 50 regions of recurring somatically acquired CNA, with the most frequently targeted genes encoding regulators of B-lymphoid development (66.8% of cases; with PAX5 targeted in 31.7% and IKZF1 in 28.6%). A CNA classifier identified a very poor outcome subgroup in the high-risk cohort (P=4.2x10-5) and was strongly associated with the presence of deletions involving IKZF1, which encodes the early lymphoid transcription factor IKAROS. This classifier, and IKZF1 deletions, also predicted poor outcome and elevated minimal residual disease at the end of induction therapy in the validation cohort. The gene expression signature of the poor outcome group was characterized by reduced expression of B lineage specific genes, and was highly related to the expressing signature of BCR-ABL1 ALL, a known high-risk ALL subtype also characterized by a high frequency of IKZF1 deletion.Somatically acquired deletions involving IKZF1 identify a very poor outcome subgroup of pediatric ALL patients. Incorporation of molecular tests to identify IKZF1 deletion in diagnostic leukemic blasts should improve the ability to accurately risk stratify patients for appropriate therapy.
Publication Title
Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 117 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), characterized by aneuploidy and poor outcome, is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two major subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations (88%), almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.
Publication Title
The genomic landscape of hypodiploid acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
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