Dataset Information

Effects of FTY720 on phospho-proteome of leukemic cells

ABSTRACT: : FTY720 (Fingolimod) is an immunosuppressive drug approved by FDA for Multiple Sclerosis (MS), that has gained attention as anti-cancer drug, thanks to its ability to disrupt the binding between the onco-protein SET and the tumor- suppressor phosphatase PP2A. We investigated FTY720 induced phospho-proteomic changes on acute myeloid leukemia cell lines carrying KMT2A-transocations. The phospho-proteomic data indicated that FTY720 treatment resulted in the down-regulation of phospho-sites associated to protein serine/threonine kinase activity, chromatin organisation and transcription. The findings support the hypothesis of a feedback loop between SET, PP2A and MYC, whereby FTY720 re-activates PP2A with an overall inhibitory effect on MYC, resulting in cell cycle arrest and apoptosis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte

DISEASE(S): Acute Leukemia

SUBMITTER: Vinothini Rajeeve

LAB HEAD: Pedro R. Cutillas

PROVIDER: PXD038288 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.

Di Mambro Antonella A Arroyo-Berdugo Yoana Y Fioretti Tiziana T Randles Michael M Cozzuto Luca L Rajeeve Vinothini V Cevenini Armando A Austin Michael J MJ Esposito Gabriella G Ponomarenko Julia J Lucas Claire M CM Cutillas Pedro P Gribben John J Williams Owen O Calle Yolanda Y Patel Bela B Esposito Maria Teresa MT

Oncogene 20231027 50

KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigat ...[more]

PMID: 37891368

Dataset Information

Effects of FTY720 on phospho-proteome of leukemic cells

Publications

SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.

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