Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia

<p>Abstract</p> <p>Background</p> <p>The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of <it>ETV6 </it>(<it>TEL</it>) and <it>RUNX1 </it>(<it>AML1</it>) genes and defines a relatively uniform category, although only some patients suffer very late relapse. <it>TEL/AML1</it>-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR.</p> <p>Results</p> <p>We compared the leukemia cell gene expression profiles of 16 <it>TEL/AML1</it>-positive ALL patients to those of 44 <it>TEL/AML1</it>-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes -<it>RUNX1, TCFL5, TNFRSF7, CBFA2T3</it>, <it>CD9</it>, <it>SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7</it>, <it>SEMA6A, CTGF, LSP1, TFPI </it>– highlighting the biology of the <it>TEL/AML1 </it>sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of <it>RUNX1 (AML1) </it>was further investigated and in one third of the patients correlated with cytogenetic findings.</p> <p>Conclusion</p> <p>Gene expression analyses of leukemia cells from 60 children with <it>TEL/AML1</it>-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the <it>TEL/AML1</it>-positive ALL sub-group.</p

Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia-0

<p><b>Copyright information:</b></p><p>Taken from "Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia"</p><p>http://www.biomedcentral.com/1471-2164/8/385</p><p>BMC Genomics 2007;8():385-385.</p><p>Published online 23 Oct 2007</p><p>PMCID:PMC2211320.</p><p></p>ifference in expression level between the -positive and the -negative ALL subclasses. SAM denotes Significant Analysis of Microarrays. Two groups of genes (according to the filters applied) were selected and functionally annotated. Nine of the 16 genes were selected for RT-PCR validation on the basis of their biological relevance

Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia-3

<p><b>Copyright information:</b></p><p>Taken from "Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia"</p><p>http://www.biomedcentral.com/1471-2164/8/385</p><p>BMC Genomics 2007;8():385-385.</p><p>Published online 23 Oct 2007</p><p>PMCID:PMC2211320.</p><p></p>ing the 14 selected genes for . Patients are segregated according to the presence or absence of the rearrangement. (B) Support tree of Set-A and Set-B patients using the 14 selected genes for . Two branches clearly distinguished -positive ALL and -negative ALL with 100% of reproducibility when resampling with replacement was conducted on experiments and genes for 100 iterations. The expression levels of the RUNX1 gene can explain the clustering of patients 9 and 17

Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia-2

<p><b>Copyright information:</b></p><p>Taken from "Five distinct biological processes and 14 differentially expressed genes characterize -positive leukemia"</p><p>http://www.biomedcentral.com/1471-2164/8/385</p><p>BMC Genomics 2007;8():385-385.</p><p>Published online 23 Oct 2007</p><p>PMCID:PMC2211320.</p><p></p>estalt pre-stored human genome gene set. Each circular area represents groups of genes, sharing common properties within relevant biological processes. Five discrete enriched GO categories are identified: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding. Enriched GO categories are represented by 16 annotated genes. Six (in bold) of these 16 genes had been previously identified, and two, in brackets, were not used for further analysis because of their tissue-specific expression patterns