Maru, Bruktawit; Messikommer, Alessandra; Huang, Linhui; Seipel, Katja; Kovecses, Olivia; Valk, Peter J M; Theocharides, Alexandre P A; Mercier, Francois E; Pabst, Thomas; McKeague, Maureen; Luedtke, Nathan W (2023). PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy. Cell reports. Medicine, 4(9), p. 101191. Elsevier 10.1016/j.xcrm.2023.101191
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Previous chemotherapy research has focused almost exclusively on apoptosis. Here, a standard frontline drug combination of cytarabine and idarubicin induces distinct features of caspase-independent, poly(ADP-ribose) polymerase 1 (PARP-1)-mediated programmed cell death "parthanatos" in acute myeloid leukemia (AML) cell lines (n = 3/10 tested), peripheral blood mononuclear cells from healthy human donors (n = 10/10 tested), and primary cell samples from patients with AML (n = 18/39 tested, French-American-British subtypes M4 and M5). A 3-fold improvement in survival rates is observed in the parthanatos-positive versus -negative patient groups (hazard ratio [HR] = 0.28-0.37, p = 0.002-0.046). Manipulation of PARP-1 activity in parthanatos-competent cells reveals higher drug sensitivity in cells that have basal PARP-1 levels as compared with those subjected to PARP-1 overexpression or suppression. The same trends are observed in RNA expression databases and support the conclusion that PARP-1 can have optimal levels for favorable chemotherapeutic responses.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Seipel, Katja, Pabst, Thomas Niklaus |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2666-3791 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Sep 2023 09:56 |
Last Modified: |
22 Sep 2023 00:16 |
Publisher DOI: |
10.1016/j.xcrm.2023.101191 |
PubMed ID: |
37683650 |
Uncontrolled Keywords: |
NAD+ ADP-ribosyltransferase 1 PAR PARP-1 acute myelomonocytic and monocytic leukemia apoptosis cancer biology caspase-independent programmed cell death nucleoside analog poly(ADP-ribose) precision medicine prognostic blood test |
BORIS DOI: |
10.48350/186200 |
URI: |
https://boris.unibe.ch/id/eprint/186200 |
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