Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma survival

ABSTRACT: Three ALCL cell lines DEL, FEPD and K299 were induced with an IRF4-specific shRNA for up to 96 hours. The three ALCL cell lines DEL, FEPD and K299 were induced with an IRF4-specific shRNA for four durations and compared with the corresponding not-induced control.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Grau

PROVIDER: E-GEOD-59747 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma.

Weilemann Andre A Grau Michael M Erdmann Tabea T Merkel Olaf O Sobhiafshar Ulduz U Anagnostopoulos Ioannis I Hummel Michael M Siegert Antje A Hayford Claudia C Madle Hannelore H Wollert-Wulf Brigitte B Fichtner Iduna I Dörken Bernd B Dirnhofer Stephan S Mathas Stephan S Janz Martin M Emre N C Tolga NC Rosenwald Andreas A Ott German G Lenz Peter P Tzankov Alexandar A Lenz Georg G

Blood 20141030 1

Anaplastic large cell lymphoma (ALCL) is a distinct entity of T-cell lymphoma that can be divided into 2 subtypes based on the presence of translocations involving the ALK gene (ALK(+) and ALK(-) ALCL). The interferon regulatory factor 4 (IRF4) is known to be highly expressed in both ALK(+) and ALK(-) ALCLs. However, the role of IRF4 in the pathogenesis of these lymphomas remains unclear. Here we show that ALCLs of both subtypes are addicted to IRF4 signaling, as knockdown of IRF4 by RNA interfe ...[more]

PMID: 25359993

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Project description:Polyamines are aliphatic polycations that have emerged as important determinants of cell growth and viability in rapidly proliferating cells, including in the pathogenic protozoan parasite Leishmania donovani. In L. donovani, the polyamine spermidine is synthesized by the successive conversion of ornithine into putrescine (catalyzed by ornithine decarboxylase or ODC) and putrescine into spermidine (catalyzed by spermidine synthase or SPDSYN). Deletion of either ODC (del-odc) or SPDSYN (del-spdsyn) from the L. donovani genome renders these parasites auxotrophic for polyamines and these mutants are impaired in their ability to survive both in culture and within the mammalian host without the addition of exogenous polyamine supplementation. Significantly, del-odc parasites immediately cease proliferation after putrescine is removed from the culture media and perish within two weeks, while spermidine starved del-spdsyn mutants, which retain intracellular putrescine pools, show a slow-growth phenotype, and persist for several weeks in culture. To elucidate the key differences within the proteome of putrescine-starved del-odc cells and spermidine-starved del-spdsyn parasites, a shotgun quantitative proteomics approach was undertaken using TMT labeling and LC-MS/MS analysis. Briefly, three biological replicates each for mid-log phase del-odc and del-spdsyn promastigotes grown in the presence of exogenous putrescine (for del-odc) or spermidine (for del-spdsyn) supplementation were washed to remove the exogenous polyamine supplementation and incubated in polyamine-free media. At 24 and 48 h, cells from each biological replicate were isolated and prepared for tandem mass tag (TMT) labeling and downstream LC-MS/MS analyses. Peptides were identified using a database generated from the reference genome of L. donovani BPK282A1 strain. Changes in relative protein abundance for the polyamine-starved del-odc and del-spdsyn cell lines at 24 and 48 h were calculated by comparing aggregate total reporter ion intensities for each protein to that of the corresponding polyamine-supplemented 0-h timepoint.

Dataset Information

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma survival

Publications

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma.

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