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Gene expression profiling of leukemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids

Aaron L Miller1 email, Spogmai Komak2 email, M Scott Webb1 email, Edward H Leiter3 email and E Brad Thompson1 email

Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA

Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA

Diabetes and Obesity, Inflammatory Bowel Diseases, The Jackson, Laboratory, Bar Harbor, ME, USA

author email corresponding author email

Cancer Cell International 2007, 7:18doi:10.1186/1475-2867-7-18

Published: 28 November 2007

Additional files

Additional file 1:

Gene expression signature for GC-sensitivity in CEM cells. Regulated transcripts from vehicle or GC-treated samples were evaluated and compared using Spotfire® and Ingenuity® bioinformatics software. Selection criteria for each gene were as follows: probe called present (Methods) on the microarray and regulated ≥ 1.2-fold (net 20% change). GC-mediated transcripts regulated in common in the same direction among sensitive CEM-C7–14 Dex (C7–14 Dx) and CVZ (C7–14 Z), CEM-C1–6 (C1–6 Dx), CEM-C1–15 CVZ (C1–15 Z), and CEM-C1–15 Dex plus FSK (C1–15 Dx+F) cells were obtained. The resulting 96 regulated genes are depicted. This list was subsequently compared to Dex-treated resistant CEM-C1–15 cells (C1–15 Dx) and to mouse thymocytes (C57/BL6 Dx). Genes linked via an Ingenuity® generated signaling pathway (Network) are designated with (symbol, closed diamond). Opposite sense regulation (Opp. R) between human and mouse is indicated by (symbol, closed circle). Bold type indicates statistically significant regulation p ≤ 0.05 between means of vehicle vs. GC-treated. Symbol, asterisk = gene "absent" by selection criteria.

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Additional file 2:

Gene expression signature for GC-sensitivity in multiple sub-types of sensitive human leukemias. Messenger RNA was extracted and regulated genes were analyzed as previously stated. A list of GC-mediated transcripts regulated in common in the same sense among sensitive CEM-C7–14 Dex (C7–14 Dx) and CVZ (C7–14 Z), CEM-C1–6 (C1–6 Dx), RS4;11 (RS4 Dx), SUP-B15 (SUP Dx), and Kasumi-1 (Kas Dx) leukemic cells was generated. These comparisons resulted in 122 regulated genes. This list was subsequently compared to Dex-treated resistant CEM-C1–15 cells (C1–15 Dx) and to mouse thymocytes (C57/BL6 Dx). Opposite sense regulation (Opp. R) between human and mouse is indicated by (symbol, closed circle). Bold type indicates statistically significant regulation p ≤ 0.05 between means of vehicle vs. GC-treated. Symbol, asterisk = gene "absent" by selection criteria.

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Additional file 3:

Genes regulated by GCs in sensitive and Dex-resistant-restored-to-sensitive human leukemias. To obtain the final list of genes regulated by GCs in all sensitive model systems, the results from Additional file 1 and Additional file 2 were combined. Depicted are 191 genes, (83 induced, symbol plus) and (108 repressed, symbol minus) genes specific to and regulated in common between the CEM and other leukemia signatures.

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Additional file 4:

Genes present on both HG_U95 Av2 and HGU133 Plus 2.0 chips. Genes regulated by GCs using selection criteria (Methods) in CEM-C7–14, CEM-C1–6, RS4;11, SUP-B15, and Kasumi-1 cells. Bold type indicates statistically significant regulation p ≤ 0.05 between means of vehicle vs. GC-treated. Blank = gene "absent" by selection criteria.

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Additional file 5:

Adult ALL vs. Pediatric ALL and AML. Genes statistically significantly regulated by Dex in adult B-cell ALL RS4;11 cells compared to other GC-sensitive pediatric leukemias. Blank = gene "absent" by selection criteria.

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Additional file 6:

Myeloid AML vs. Lymphoid ALL. Genes statistically significantly regulated by Dex in Kasumi-1 AML cells compared to GC-sensitive lymphoid leukemic cells. Blank = gene "absent" by selection criteria.

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Additional file 7:

T-cell ALL vs. B-cell ALL. Genes regulated in common in the same sense by Dex in GC-sensitive T-cell ALL CEM-C7–14, CEM-C1–6 and GC-sensitive B-cell ALL RS4;11, SUP-B15 cells. Bold type indicates statistically significant regulation p ≤ 0.05 between means of vehicle vs. GC-treated.

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Additional file 8:

Pediatric T-cell ALL vs. Pediatric B-cell ALL. Genes regulated in common in the same sense by Dex in T-cell ALL CEM-C7–14, CEM-C1–6, and B-cell SUP-B15 cells. Bold type indicates statistically significant regulation p ≤ 0.05 between means of vehicle vs. GC-treated.

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Additional file 9:

Pediatric B-cell ALL vs. Adult B-cell ALL. Genes statistically significantly regulated by Dex in pediatric SUP-B15 cells compared to adult RS4;11 cells. Blank = gene "absent" by selection criteria.

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