The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Association of CYP 3 A 4 genotype with treatment-related leukemia
Open accessAbstract
Epipodophyllotoxins are associated with leukemias characterized by translocations of the MLL gene at chromosome band 11q23 and other translocations. Cytochrome P450 (CYP) 3A metabolizes epipodophyllotoxins and other chemotherapeutic agents. CYP3A metabolism generates epipodophyllotoxin catechol and quinone metabolites, which could damage DNA. There is a polymorphism in the 5′ promoter region of the CYP3A4 gene ( CYP3A4-V ) that might alter the metabolism of anticancer drugs. We examined 99 de novo and 30 treatment-related leukemias with a conformation-sensitive gel electrophoresis assay for the presence of the CYP3A4-V . In all treatment-related cases, there was prior exposure to one or more anticancer drugs metabolized by CYP3A. Nineteen of 99 de novo (19%) and 1 of 30 treatment-related (3%) leukemias carried the CYP3A4-V ( P = 0.026; Fisher’s Exact Test, FET). Nine of 42 de novo leukemias with MLL gene translocations (21%), and 0 of 22 treatment-related leukemias with MLL gene translocations carried the CYP3A4-V ( P = 0.016, FET). This relationship remained significant when 19 treatment-related leukemias with MLL gene translocations that followed epipodophyllotoxin exposure were compared with the same 42 de novo cases ( P = 0.026, FET). These data suggest that individuals with CYP3A4-W genotype may be at increased risk for treatment-related leukemia and that epipodophyllotoxin metabolism by CYP3A4 may contribute to the secondary cancer risk. The CYP3A4-W genotype may increase production of potentially DNA-damaging reactive intermediates. The variant may decrease production of the epipodophyllotoxin catechol metabolite, which is the precursor of the potentially DNA-damaging quinone.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hayes, J. D., & Pulford, D. J. (1995) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239509083491 · Cited by 3,464
REPAIR OF OXIDATIVE DAMAGE TO DNA: Enzymology and Biology
Demple, B., & Harrison, L. (1994) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.63.070194.004411 · Cited by 1,495
The Human Hepatic Cytochromes P450 Involved in Drug Metabolism
Wrighton, S. A., & Stevens, J. C. (1992) · Critical Reviews in Toxicology · doi:10.3109/10408449209145319 · Cited by 944
DNA glycosylases in the base excision repair of DNA
KROKAN, H. E., STANDAL, R., & SLUPPHAUG, G. (1997) · Biochemical Journal · doi:10.1042/bj3250001 · Cited by 859
Gu, Y., Nakamura, T., Alder, H., Prasad, R., Canaani, O., Cimino, G., Croce, C. M., & Canaani, E. (1992) · Cell · doi:10.1016/0092-8674(92)90603-a · Cited by 824
Molecular origin of cancer: Catechol estrogen-3,4-quinones as endogenous tumor initiators
Cavalieri, E. L., Stack, D. E., Devanesan, P. D., Todorovic, R., Dwivedy, I., Higginbotham, S., Johansson, S. L., Patil, K. D., Gross, M. L., Gooden, J. K., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10937 · Cited by 727
Acute Myeloid Leukemia in Children Treated with Epipodophyllotoxins for Acute Lymphoblastic Leukemia
Pui, C.-H., Ribeiro, R. C., Hancock, M. L., Rivera, G. K., Evans, W. E., Raimondi, S. C., Head, D. R., Behm, F. G., Mahmoud, M. H., Sandlund, J. T., et al. (1991) · New England Journal of Medicine · doi:10.1056/nejm199112123252402 · Cited by 713
Homology-directed repair is a major double-strand break repair pathway in mammalian cells
Liang, F., Han, M., Romanienko, P. J., & Jasin, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5172 · Cited by 649
Chang, T. K. H., Weber, G. F., Crespi, C. L., & Waxman, D. J. (1993) · PubMed · Cited by 545
Second malignant neoplasms in children: an update from the Late Effects Study Group.
Meadows, A. T., Baum, E., Fossati-Bellani, F., Green, D., Jenkin, R. D., Marsden, B., Nesbit, M., Newton, W., Oberlin, O., & Sallan, S. G. (1985) · Journal of Clinical Oncology · doi:10.1200/jco.1985.3.4.532 · Cited by 481
Cited by
Genetic contribution to variable human CYP3A-mediated metabolism
Lamba, J. K., Lin, Y. S., Schuetz, E. G., & Thummel, K. E. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00066-2 · Cited by 990
Hesselink, D. (2003) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(03)00168-1 · Cited by 655
Molecular Basis of Ethnic Differences in Drug Disposition and Response
Xie, H.-G., Kim, R. B., Wood, A. J., & Stein, C. M. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.815 · Cited by 600
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation
Zanger, U. M., Turpeinen, M., Klein, K., & Schwab, M. (2008) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-008-2291-6 · Cited by 593
Cytochrome P450 3A: Ontogeny and Drug Disposition
de Wildt, S. N., Kearns, G. L., Leeder, J. S., & van den Anker, J. N. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199937060-00004 · Cited by 586
Metadata
- Authors
- Felix, C. A., Walker, A. H., Lange, B. J., Williams, T. M., Winick, N. J., Cheung, N.-K. V., Lovett, B. D., Nowell, P. C., Blair, I. A., & Rebbeck, T. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-10-27
- Volume
- 95
- Issue
- 22
- Pages
- 13176-13181
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2072467180
- Cited by
- 310
- References
- 44
- FWCI
- 19.78
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Association of CYP 3 A 4 genotype with treatment-related leukemia. https://app.cochat.ai/papers/10.1073/pnas.95.22.13176
- The paper
- Felix, C. A., Walker, A. H., Lange, B. J., Williams, T. M., Winick, N. J., Cheung, N.-K. V., Lovett, B. D., Nowell, P. C., Blair, I. A., & Rebbeck, T. R. (1998). Association of CYP 3 A 4 genotype with treatment-related leukemia. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.22.13176
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
