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Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status
B. Kubesova, S. Pavlova, J. Malcikova, J. Kabathova, L. Radova, N. Tom, B. Tichy, K. Plevova, B. Kantorova, K. Fiedorova, M. Slavikova, V. Bystry, J. Kissova, B. Gisslinger, H. Gisslinger, M. Penka, J. Mayer, R. Kralovics, S. Pospisilova, M. Doubek,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NV16-29447A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Open Access Digital Library od 1997-01-01
Nursing & Allied Health Database (ProQuest) od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest) od 2000-01-01 do Před 1 rokem
Odkazy
PubMed
28744014
DOI
10.1038/leu.2017.230
Knihovny.cz E-zdroje
- MeSH
- akutní myeloidní leukemie farmakoterapie genetika MeSH
- alely MeSH
- dospělí MeSH
- frekvence genu účinky léků genetika MeSH
- hydroxymočovina aplikace a dávkování MeSH
- Janus kinasa 2 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutace účinky léků genetika MeSH
- myeloproliferativní poruchy farmakoterapie genetika MeSH
- nádorový supresorový protein p53 genetika MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2-16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.
CeMM Research Center for Molecular Medicine of Austrian Academy of Sciences Vienna Austria
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Clinical Hematology Faculty of Medicine Masaryk University Brno Czech Republic
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