ArrayExpress Uploader0145ETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLETV6-RUNX1 B-precursor ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with miscellaneous karyotypeHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLHigh hyperdiploid B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLTCF3-PBX1 B-precursor ALLBCR-ABL1 B-precursor ALLBCR-ABL1 B-precursor ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALLT-lineage ALL and early thymic progenitor immunophenotypeT-lineage ALL and early thymic progenitor immunophenotypeT-lineage ALL with MLL rearrangementB-precursor ALL with pseudodiploid karyotypeB-precursor ALL with pseudodiploid karyotypeB-precursor ALL with pseudodiploid karyotypeB-precursor ALL with miscellaneous karyotypeB-precursor ALL with pseudodiploid karyotypeB-precursor ALL with hypodiploid karyotypetumor with alteration of ERGtumor with alteration of ERGchildhood ALL with CRLF2 rearrangementchildhood ALL with CRLF2 rearrangementchildhood ALL with CRLF2 rearrangementchildhood ALL with CRLF2 rearrangementchildhood ALL with CRLF2 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with BCR-ABL1 rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with MLL rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with ETV6-RUNX1 rearrangementchildhood ALL with TCF3-PBX1 rearrangementchildhood ALL with TCF3-PBX1 rearrangementchildhood ALL with high hyperdiploid karyotypearrayexpress_sid3Notch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T cell acute lymphoblastic...21224467E-GEOD-26366/profile/8773/arrayexpressuploader1206acute lymphoblastic leukemiacancercellleukemialymphoblastic leukemianotchproteinDec.12, 2014Falsenotchhes1-mediated-parp1-activation-a-cell-type-spE-GEOD-26366_A-AFFY-33Notch/HES1-mediated PARP1 activation: A cell-type specific mechanism for tumor suppressionJun.10, 2014Notch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T cell acute lymphoblastic leukemia (T-ALL), where Notch activation promotes leukemogenesis, induction of Notch signaling in B-ALL leads to growth arrest and apoptosis. The Notch target Hairy/Enhancer of Split1 (HES1) is sufficient to reproduce this tumor suppressor phenotype in B-ALL, however the mechanism is not yet known. Here we report that HES1 regulates pro-apoptotic signals via the novel interacting protein Poly ADP-Ribose Polymerase1 (PARP1) in a cell type-specific manner. The interaction of HES1 with PARP1 inhibits HES1 function, induces PARP1 activation and results in PARP1 cleavage in B-ALL. HES1-induced PARP1 activation leads to self-ADP ribosylation of PARP1, consumption of NAD+, diminished ATP levels, and translocation of the Apoptosis Inducing Factor (AIF) from mitochondria to the nucleus, resulting in apoptosis in B-ALL, but not T-ALL. Importantly, induction of Notch signaling via the Notch agonist peptide DSL can reproduce these events and leads to BALL apoptosis. The novel interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis. This mechanism reveals a cell type-specific pro-apoptotic pathway which may lead to Notch agonist-based cancer therapeutics. Study involved the gene expression profiling of human acute lymphoblastic leukemia samples, and comparison of the levels of expression NOTCH1 pathway genes and targets across ALL subtypeshttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26366humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26366/samples/