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Akademický článek

Alternative splicing of the tumor suppressor ASPP2 results in a stress-inducible, oncogenic isoform prevalent in acute leukemiaResearch in context

Autor: Marcus Matthias Schittenhelm, Bianca Walter, Vasileia Tsintari, Birgit Federmann, Mihada Bajrami Saipi, Figen Akmut, Barbara Illing, Ulrike Mau-Holzmann, Falko Fend, Charles Darin Lopez, Kerstin Maria Kampa-Schittenhelm

Publikováno v: EBioMedicine, Vol 42, Iss , Pp 340-351 (2019)

Background: Apoptosis-stimulating Protein of TP53-2 (ASPP2) is a tumor suppressor enhancing TP53-mediated apoptosis via binding to the TP53 core domain. TP53 mutations found in cancers disrupt ASPP2 binding, arguing for an important role of ASPP2 in

Externí odkaz: https://doaj.org/article/162a0dcf7af743ecb55394431c13be11

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Alternative splicing of the tumor suppressor ASPP2 results in a stress-inducible, oncogenic isoform prevalent in acute leukemia

Autor: Bianca Walter, Marcus M Schittenhelm, Kerstin M Kampa-Schittenhelm, Falko Fend, Mihada Bajrami Saipi, Birgit Federmann, Vasileia Tsintari, Charles D. Lopez, Ulrike A. Mau-Holzmann, Figen Akmut, Barbara Illing

Publikováno v: EBioMedicine. 42:340-351

Background Apoptosis-stimulating Protein of TP53-2 (ASPP2) is a tumor suppressor enhancing TP53-mediated apoptosis via binding to the TP53 core domain. TP53 mutations found in cancers disrupt ASPP2 binding, arguing for an important role of ASPP2 in T

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2046f8309a575fa59feabef21112b5ad
https://doi.org/10.1016/j.ebiom.2019.03.028

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Epigenetic activation of O-linked β-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia

Autor: E. Schleicher, I. Bonzheim, S.T. Dreher, T. Ganief, Marcus M. Schittenhelm, L. Haeusser, M. Bonin, T. Haverkamp, W. Vogel, Barbara Illing, H.J. Bühring, Gunnar Blumenstock, Figen Akmut, Kerstin M Kampa-Schittenhelm, Vasileia Tsintari, Ulrike A. Mau-Holzmann

Publikováno v: EBioMedicine
EBioMedicine, Vol 54, Iss, Pp-(2020)

Background: Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy – now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5159df8cef300ddbb450e4ce2611020a
https://pubmed.ncbi.nlm.nih.gov/32272438

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Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia

Autor: Figen Akmut, Katharina Henriette Rasp, Kerstin M Kampa-Schittenhelm, Barbara Illing, Hartmut Döhner, Michael Heinrich, Marcus M Schittenhelm, Konstanze Döhner

Publikováno v: Molecular Cancer

Background Dysregulation of the PI3Kinase/AKT pathway is involved in the pathogenesis of many human malignancies. In acute leukemia, the AKT pathway is frequently activated, however mutations in the PI3K/AKT pathway are uncommon. In some cases, const

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ed36dc477e2ee3285b173be72c373d6
https://pubmed.ncbi.nlm.nih.gov/23705826

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Gain-of-Function KIT Mutations Sensitize the Mutant Isoform to the Type I Tyrosine Kinase Inhibitor Crenolanib: A Rationale for the Therapeutic Use in Systemic Mastocytosis (SM) and Core Binding Factor Leukemias (CBFL)

Autor: Barbara Illing, Figen Akmut, Lothar Kanz, Kerstin M Kampa-Schittenhelm, Marcus M Schittenhelm, Julia Frey, Abhijit Ramachandran, Katja Schuster

Publikováno v: Blood. 124:2230-2230

Activating mutations of the class III receptor tyrosine kinases FLT3 and KIT are associated with certain human neoplasms, including hematologic malignancies, i.e. the majority of patients with systemic mast cell disorders (KIT) and subsets of patient

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::0cec2dd9c61d4643bb529ef163957214
https://doi.org/10.1182/blood.v124.21.2230.2230

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ASPP2 Attenuation Is an Early Step in Leukemogenesis Facilitating Acquisition of Mutations

Autor: Figen Akmut, Marcus M Schittenhelm, Barbara Illing, Charles D. Lopez, Kerstin M Kampa-Schittenhelm

Publikováno v: Blood. 124:2221-2221

Inactivation of the p53 pathway is an universal event in human cancers. As p53 mutations are rare in de novo acute leukemias, the p53-pathway must be inactivated by other mechanisms instead. The Apoptosis stimulating Protein of p53-2 (ASPP2) is a hap

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::745b3629814ec9b4e106489dec9acdcc
https://doi.org/10.1182/blood.v124.21.2221.2221

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Heatshockproteins-60 and 90 Are Overexpressed In Leukemia Stem Cells and Stabilize Oncogene Signaling

Autor: Kerstin M Kampa-Schittenhelm, Tanja Grandl, Figen Akmut, Barbara Illing, Marcus M Schittenhelm

Publikováno v: Blood. 122:3952-3952

Introduction Activating mutations of the KIT class III receptor tyrosine kinase (TK) are associated with the pathophysiology of acute leukemia, especially core binding factor leukemia (CBFL), and systemic mastocytosis (SM). Despite considerable antip

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::0b205a2b165468c3f425e04622759a2c
https://doi.org/10.1182/blood.v122.21.3952.3952

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Identification Of C-Terminal Truncated Splice Variants Of The Apoptosis-Stimulating Protein Of p53-2 (ASPP2) In Acute Leukemia Lacking The p53-Binding Site

Autor: Kerstin M Kampa-Schittenhelm, Michael Walter, Marcus M Schittenhelm, Charles D. Lopez, Barbara Illing, Figen Akmut

Publikováno v: Blood. 122:1270-1270

Apoptosis seems to be a major means by which p53 suppresses tumorigenesis in hematopoietic cells. While loss-of-function mutations in p53 are frequently found in most neoplasms, non-complex karyotype acute leukemias are typically p53 wildtype and the

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::4db0fed0723340139b2eda3b6634f3f3
https://doi.org/10.1182/blood.v122.21.1270.1270

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Induction Of Apoptosis By The Dual PI3K/Mtor Inhibitor NVP-BEZ235 Is Impaired By a Profound G1/G0 Arrest In Acute Leukemia Which Can Be Overcome By Combination Approaches

Autor: Figen Akmut, Barbara Illing, Kerstin M Kampa-Schittenhelm, Marcus M Schittenhelm

Publikováno v: Blood. 122:3856-3856

Introduction Constitutive phosphorylation of AKT is frequently found in acute leukemia. In a proportion of patients, activation of the PI3K/AKT pathway can be linked to gain-of-function tyrosine kinase mutations. We have previously shown that TKI onl

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::7e01cdaa1c75c93cbaa1587174c0887d
https://doi.org/10.1182/blood.v122.21.3856.3856

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Methylation Of The 5’UTR Of Apoptosis Stimulating Protein Of p53-2 (ASPP2) Impairs Gene Expression and Associates With Aggressive Disease and Therapy Failure In Acute Leukemia

Autor: Gunnar Blumenstock, Charles D. Lopez, Konstanze Döhner, Marcus M Schittenhelm, Kerstin M Kampa-Schittenhelm, Barbara Illing, Figen Akmut

Publikováno v: Blood. 122:3770-3770

Introduction Inactivation of the p53 pathway is a frequent event in human cancers promoting tumorigenesis and resistance to chemotherapy. Inactivating p53 mutations are uncommon in non-complex karyotype leukemias suggesting that the p53-pathway must

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::9a4a0a2aa3cfd5c1ea7dba45660a8d9f
https://doi.org/10.1182/blood.v122.21.3770.3770

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