ArticleOncogene2005
Caspase-8L expression protects CD34+ hematopoietic progenitor cells and leukemic cells from CD95-mediated apoptosis.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- DNA damage response and preleukemic fusion genes induced by ionizing radiation in umbilical cord blood hematopoietic stem cells.Scientific reports · 2020Article
- Splicing machinery genomics events in acute myeloid leukaemia (AML): in search for therapeutic targets, diagnostic and prognostic biomarkers.American journal of cancer research · 2020Review
- The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer.Frontiers in molecular biosciences · 2018Review
- Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases.BioMed research international · 2018Review
- Hematopoietic stem/progenitor cells are less prone to undergo apoptosis than lymphocytes despite similar DNA damage response.Oncotarget · 2017Article
- Aberrant splicing and drug resistance in AML.Journal of hematology & oncology · 2016Review
- New basal cell carcinoma susceptibility loci.Nature communications · 2015Article
- Identification of a secondary promoter of CASP8 and its related transcription factor PURα.International journal of oncology · 2014Article
- Harnessing of Programmed Necrosis for Fighting against Cancers.Biomolecules & therapeutics · 2014Review
- Deregulation of apoptotic factors Bcl-xL and Bax confers apoptotic resistance to myeloid-derived suppressor cells and contributes to their persistence in cancer.The Journal of biological chemistry · 2013Article
- Regulation of cell death in cancer-possible implications for immunotherapy.Frontiers in oncology · 2013Article
- Oncogenic alternative splicing switches: role in cancer progression and prospects for therapy.International journal of cell biology · 2013Review
- Alternative splicing and its impact as a cancer diagnostic marker.Genomics & informatics · 2012Article
- A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants.Blood cancer journal · 2011Article
- Caspases and cancer.Cell death and differentiation · 2011Review
- A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.PloS one · 2011Article
- The enigmatic roles of caspases in tumor development.Cancers · 2010Article
- Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A.The Journal of biological chemistry · 2010Article
- Evasion of apoptosis as a cellular stress response in cancer.International journal of cell biology · 2010Article
- MnSOD protects colorectal cancer cells from TRAIL-induced apoptosis by inhibition of Smac/DIABLO release.Oncogene · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of sensitivity or resistance for apoptosis by death receptor ligand systems is a key control mechanism in the hematopoietic system. Dysfunctional or deregulated apoptosis can potentially contribute to the development of immune deficiencies, autoimmune diseases, and leukemia. Control of homeostasis starts at the level of hematopoietic stem cells (HSC). To this end, we found that CD34+ hematopoietic progenitor cells are constitutively resistant to CD95-mediated apoptosis and cannot be sensitized during short-term culture to death receptor-mediated apoptosis by cytokines. Detailed analysis of the death machinery revealed that CD34+ cells do not express caspase-8a/b, a crucial constituent of the death-inducing signaling complex (DISC) of death receptors. Instead, we found a smaller splice variant termed caspase-8L to be present in HSC. Forced expression of caspase-8L using a recombinant lentiviral vector was able to protect hematopoietic cells from death receptor-induced apoptosis even in the presence of caspase-8a/b. Furthermore, we found that caspase-8L is recruited to the DISC after CD95 triggering, thereby preventing CD95 from connecting to the caspase cascade. These results demonstrate an antiapoptotic function of caspase-8L and suggest a critical role as apoptosis regulator in HSC. Similar to CD34+ HSC, stem cell-derived leukemic blasts from AML(M0) patients only expressed caspase-8L. Additionally we found, caspase-8L expression in several AML and ALL samples. Thus, caspase-8L expression might explain constitutive resistance to CD95-mediated apoptosis in CD34+ progenitor cells and might participate in the development of stem cell-derived and other leukemias by providing protection from regulatory apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.