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1000 Titel
  • Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia
1000 Autor/in
  1. Becker, Heiko |
  2. Pfeifer, Dietmar |
  3. Ihorst, Gabriele |
  4. Pantic, Milena |
  5. Wehrle, Julius |
  6. Rüter, Björn H. |
  7. Bullinger, Lars |
  8. Hackanson, Björn |
  9. Germing, Ulrich |
  10. Kuendgen, Andrea |
  11. Platzbecker, Uwe |
  12. Döhner, Konstanze |
  13. Ganser, Arnold |
  14. Hagemeijer, Anne |
  15. Wijermans, Pierre W. |
  16. Döhner, Hartmut |
  17. Duyster, Justus |
  18. Lübbert, Michael |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-06
1000 Erschienen in
1000 Quellenangabe
  • 99(7):1551-1560
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00277-020-04082-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316846/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.
1000 Sacherschließung
lokal Smith-Magenis Syndrome/epidemiology [MeSH]
lokal Aged, 80 and over [MeSH]
lokal Aged [MeSH]
lokal Mutations
lokal Karyotype [MeSH]
lokal Germany/epidemiology [MeSH]
lokal DNA Mutational Analysis [MeSH]
lokal TP53
lokal Original Article
lokal Acute myeloid leukemia
lokal Decitabine
lokal Monosomy
lokal Male [MeSH]
lokal Leukemia, Myeloid, Acute/genetics [MeSH]
lokal Chromosome Deletion [MeSH]
lokal Smith-Magenis Syndrome/genetics [MeSH]
lokal Female [MeSH]
lokal Mutation [MeSH]
lokal Clonal Evolution/genetics [MeSH]
lokal Monosomy/genetics [MeSH]
lokal Humans [MeSH]
lokal Monosomy/diagnosis [MeSH]
lokal Clonal Evolution/drug effects [MeSH]
lokal Survival Analysis [MeSH]
lokal Middle Aged [MeSH]
lokal Tumor Suppressor Protein p53/genetics [MeSH]
lokal Decitabine/therapeutic use [MeSH]
lokal Smith-Magenis Syndrome/diagnosis [MeSH]
lokal Leukemia, Myeloid, Acute/epidemiology [MeSH]
lokal Chromosomes, Human, Pair 17/genetics [MeSH]
lokal Karyotyping [MeSH]
lokal Leukemia, Myeloid, Acute/drug therapy [MeSH]
lokal Leukemia, Myeloid, Acute/pathology [MeSH]
lokal AML
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-6919-4048|https://frl.publisso.de/adhoc/uri/UGZlaWZlciwgRGlldG1hcg==|https://frl.publisso.de/adhoc/uri/SWhvcnN0LCBHYWJyaWVsZQ==|https://frl.publisso.de/adhoc/uri/UGFudGljLCBNaWxlbmE=|https://frl.publisso.de/adhoc/uri/V2VocmxlLCBKdWxpdXM=|https://frl.publisso.de/adhoc/uri/UsO8dGVyLCBCasO2cm4gSC4=|https://frl.publisso.de/adhoc/uri/QnVsbGluZ2VyLCBMYXJz|https://frl.publisso.de/adhoc/uri/SGFja2Fuc29uLCBCasO2cm4=|https://frl.publisso.de/adhoc/uri/R2VybWluZywgVWxyaWNo|https://frl.publisso.de/adhoc/uri/S3VlbmRnZW4sIEFuZHJlYQ==|https://frl.publisso.de/adhoc/uri/UGxhdHpiZWNrZXIsIFV3ZQ==|https://frl.publisso.de/adhoc/uri/RMO2aG5lciwgS29uc3Rhbnpl|https://frl.publisso.de/adhoc/uri/R2Fuc2VyLCBBcm5vbGQ=|https://frl.publisso.de/adhoc/uri/SGFnZW1laWplciwgQW5uZQ==|https://frl.publisso.de/adhoc/uri/V2lqZXJtYW5zLCBQaWVycmUgVy4=|https://frl.publisso.de/adhoc/uri/RMO2aG5lciwgSGFydG11dA==|https://frl.publisso.de/adhoc/uri/RHV5c3RlciwgSnVzdHVz|https://frl.publisso.de/adhoc/uri/TMO8YmJlcnQsIE1pY2hhZWw=
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1000 Erstellt am 2023-11-17T05:04:52.622+0100
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