Attenuated Expression of Apoptosis Stimulating Protein of p53-2 (ASPP2) in Human Acute Leukemia Is Associated with Therapy Failure

• DOI: 10.1371/journal.pone.0080193
• Publication Date: 2013-11-27T23:50:55Z
• Authors: Marcus M. Schitte...; Barbara Illing; Figen Ahmut; Katharina Henriet...; Gunnar Blumenstock; Konstanze Döhner; Charles D. Lopez; Kerstin M. Kampa-...
• Keywords: Adult; Male; 0301 basic medicine; Science; Antineoplastic Agents; Apoptosis; Young Adult; 03 medical and health sciences; Cell Line, Tumor; Humans; RNA, Messenger; Treatment Failure; Aged; Gene Expression Regulation, Leukemic; Q; R; 500; Middle Aged; 3. Good health; Leukemia, Myeloid, Acute; Treatment Outcome; Gene Knockdown Techniques; Medicine; Female; Apoptosis Regulatory Proteins; Research Article

Inactivation of the p53 pathway is a universal event in human cancers and promotes tumorigenesis resistance to chemotherapy. Inactivating mutations are uncommon non-complex karyotype leukemias, thus p53-pathway must be inactivated by other mechanisms. The Apoptosis Stimulating Protein p53-2 (ASPP2) damage-inducible p53-binding protein that enhances apoptosis at least part through p53-mediated pathway. We have previously shown, ASPP2 an independent haploinsufficient tumor suppressor vivo. Now, we reveal expression significantly attenuated acute myeloid lymphoid leukemia – especially patients with unfavorable prognostic risk profile who fail induction In line, knock down expressing cell lines native leukemic blasts attenuates damage-induced apoptosis. Furthermore, cultured derived from high-risk leukemias induce upon anthracycline treatment. mechanisms dysregulation unknown. provide evidence attenuation caused hypermethylation promoter 5′UTR regions blasts. Together, our results suggest contributes biology should further explored as potential and/or predictive biomarker monitor therapy responses leukemia.