ArticleOncogene2005
Melphalan-induced apoptosis in multiple myeloma cells is associated with a cleavage of Mcl-1 and Bim and a decrease in the Mcl-1/Bim complex.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 71 citations in OpenAlex.
- Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.Cell reports · 2024Article
- Diallyl disulfide synergizes with melphalan to increase apoptosis and DNA damage through elevation of reactive oxygen species in multiple myeloma cells.Annals of hematology · 2024Article
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- BCLXL PROTAC degrader DT2216 targets secondary plasma cell leukemia addicted to BCLXL for survival.Frontiers in oncology · 2023Article
- MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents.Journal of hematology & oncology · 2020Review
- RIPK1-mediated immunogenic cell death promotes anti-tumour immunity against soft-tissue sarcoma.EMBO molecular medicine · 2020Article
- [Effect of CPT combined with melphalan on proliferation of human multiple myeloma cells RPMI8226 and its mechanism].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2019Article
- Article
- Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma.RNA biology · 2015Article
- Article
- The VTLISFG motif in the BH1 domain plays a significant role in regulating the degradation of Mcl-1.FEBS open bio · 2014Article
- Article
- Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells.PloS one · 2013Article
- Identification of novel SAR properties of the Jak2 small molecule inhibitor G6: significance of the para-hydroxyl orientation.Bioorganic & medicinal chemistry letters · 2012Article
- A46, a benzothiophene-derived compound, suppresses Jak2-mediated pathologic cell growth.Experimental hematology · 2012Article
- Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma.British journal of haematology · 2011Article
- PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells.British journal of cancer · 2011Article
- Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim.Oncogene · 2010Article
- Reactive oxygen species are not required for an arsenic trioxide-induced antioxidant response or apoptosis.The Journal of biological chemistry · 2009Article
- Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa.Molecular cancer therapeutics · 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is a rapidly fatal plasma-cell malignancy that evolves mainly in the bone marrow. Melphalan is widely used to treat patients with MM but as yet its mechanisms of action are poorly documented. In the current study, we demonstrate that melphalan induces a drastic downregulation of Mcl-1L, Bcl-x(L) and BimEL in human melphalan-sensitive myeloma cells while the most potent proapoptotic isoforms, BimL and S, are affected to a lesser extent. Moreover, Mcl-1L and BimEL disappearance is associated with the generation of proapoptotic cleaved forms generated by a caspase cleavage. In myeloma cells, we have previously shown that Mcl-1 neutralizes the proapoptotic function of Bim and therefore, prevents the activation of death effectors. In this study, we demonstrate that melphalan disrupts the Mcl-1/Bim complex whereas the Bcl-2/Bim complex is not modified. The disappearance of full length Mcl-1 allows the release of Bim isoforms, particularly L and S, which can exert their proapoptotic function and leads to Bax activation and cytochrome c release. Thus, we can hypothesize that the cleaved 26 kDa proapoptotic Mcl-1 and the 19 and 12 kDa of Bim, generated during melphalan treatment could contribute to the amplification loop of 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.