ArticleMolecular and cellular biology1997
DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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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.
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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.
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Who cites it
70 citing papers in PubMed, 179 citations in OpenAlex.
- Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation.Leukemia · 2010Trial
- A complex mutational signature generated by cytarabine resistance.NAR cancer · 2026Article
- Apoptosis-driven chromosomal rearrangements in cancer: CAD cleavage, nuclear architecture, and microhomology-mediated end joining.Oncogenesis · 2026Review
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- The KMT2A recombinome of acute leukemias in 2023.Leukemia · 2023Article
- DNA fragility at theOpen biology · 2023Review
- The insecticides permethrin and chlorpyrifos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells.Haematologica · 2022Article
- New insights into the activities and toxicities of the old anticancer drug doxorubicin.The FEBS journal · 2021Review
- Etoposide, an anticancer drug involved in therapy-related secondary leukemia: Enzymes at play.Translational oncology · 2021Review
- Mutagenic Consequences of Sublethal Cell Death Signaling.International journal of molecular sciences · 2021Review
- Anastasis: recovery from the brink of cell death.Royal Society open science · 2018Review
- Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in nasopharyngeal epithelial cells: implications in chromosome rearrangement.BMC cancer · 2018Article
- The MLL recombinome of acute leukemias in 2017.Leukemia · 2018Article
- Article
- Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine.Cell death & disease · 2017Article
- Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma.Cell & bioscience · 2016Article
- Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress.Oncogene · 2015Article
- Topoisomerase-mediated chromosomal break repair: an emerging player in many games.Nature reviews. Cancer · 2015Review
- Leukemogenic rearrangements at the mixed lineage leukemia gene (MLL)-multiple rather than a single mechanism.Frontiers in cell and developmental biology · 2015Review
- Topoisomerase II and leukemia.Annals of the New York Academy of Sciences · 2014Review
10 more citing papers are in PubMed but not listed here.
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 3 institutions in 2 countries.
Funding
Abstract
A distinct population of therapy-related acute myeloid leukemia (t-AML) is strongly associated with prior administration of topoisomerase II (topo II) inhibitors. These t-AMLs display distinct cytogenetic alterations, most often disrupting the MLL gene on chromosome 11q23 within a breakpoint cluster region (bcr) of 8.3 kb. We recently identified a unique site within the MLL bcr that is highly susceptible to DNA double-strand cleavage by classic topo II inhibitors (e.g., etoposide and doxorubicin). Here, we report that site-specific cleavage within the MLL bcr can be induced by either catalytic topo II inhibitors, genotoxic chemotherapeutic agents which do not target topo II, or nongenotoxic stimuli of apoptotic cell death, suggesting that this site-specific cleavage is part of a generalized cellular response to an apoptotic stimulus. We also show that site-specific cleavage within the MLL bcr can be linked to the higher-order chromatin fragmentation that occurs during the initial stages of apoptosis, possibly through cleavage of DNA loops at their anchorage sites to the nuclear matrix. In addition, we show that site-specific cleavage is conserved between species, as specific DNA cleavage can also be demonstrated within the murine MLL locus. Lastly, site-specific cleavage during apoptosis can also be identified at the AML1 locus, a locus which is also frequently involved in chromosomal rearrangements present in t-AML patients. In conclusion, these results suggest the potential involvement of higher-order chromatin fragmentation which occurs as a part of a generalized apoptotic response in a mechanism leading to chromosomal translocation of the MLL and AML1 genes and subsequent t-AML.
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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.