| KUBEŠOVÁ, Blanka, Šárka PAVLOVÁ, Jitka MALČÍKOVÁ, Jitka KABÁTHOVÁ, Lenka RADOVÁ, Nikola TOM, Boris TICHÝ, Karla PLEVOVÁ, Barbara KANTOROVÁ, Kristýna FIEDOROVÁ, M. SLAVIKOVA, Vojtěch BYSTRÝ, Jarmila KISSOVÁ, B. GISSLINGER, H. GISSLINGER, Miroslav PENKA, Jiří MAYER, R. KRALOVICS, Šárka POSPÍŠILOVÁ and Michael DOUBEK. Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status (Low- burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status.). Leukemia. London: Nature Publishing Group, 2018, vol. 32, No 2, p. 450-461. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/leu.2017.230. |
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@article{1404544,
author = {Kubešová, Blanka and Pavlová, Šárka and Malčíková, Jitka and Kabáthová, Jitka and Radová, Lenka and Tom, Nikola and Tichý, Boris and Plevová, Karla and Kantorová, Barbara and Fiedorová, Kristýna and Slavikova, M. and Bystrý, Vojtěch and Kissová, Jarmila and Gisslinger, B. and Gisslinger, H. and Penka, Miroslav and Mayer, Jiří and Kralovics, R. and Pospíšilová, Šárka and Doubek, Michael},
article_location = {London},
article_number = {2},
doi = {http://dx.doi.org/10.1038/leu.2017.230},
keywords = {TP53 mutations; myeloproliferative neoplasms},
language = {eng},
issn = {0887-6924},
journal = {Leukemia},
title = {Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status},
volume = {32},
year = {2018}
}
TY - JOUR
ID - 1404544
AU - Kubešová, Blanka - Pavlová, Šárka - Malčíková, Jitka - Kabáthová, Jitka - Radová, Lenka - Tom, Nikola - Tichý, Boris - Plevová, Karla - Kantorová, Barbara - Fiedorová, Kristýna - Slavikova, M. - Bystrý, Vojtěch - Kissová, Jarmila - Gisslinger, B. - Gisslinger, H. - Penka, Miroslav - Mayer, Jiří - Kralovics, R. - Pospíšilová, Šárka - Doubek, Michael
PY - 2018
TI - Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status
JF - Leukemia
VL - 32
IS - 2
SP - 450-461
EP - 450-461
PB - Nature Publishing Group
SN - 08876924
KW - TP53 mutations
KW - myeloproliferative neoplasms
N2 - 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.
ER -
KUBEŠOVÁ, Blanka, Šárka PAVLOVÁ, Jitka MALČÍKOVÁ, Jitka KABÁTHOVÁ, Lenka RADOVÁ, Nikola TOM, Boris TICHÝ, Karla PLEVOVÁ, Barbara KANTOROVÁ, Kristýna FIEDOROVÁ, M. SLAVIKOVA, Vojtěch BYSTRÝ, Jarmila KISSOVÁ, B. GISSLINGER, H. GISSLINGER, Miroslav PENKA, Jiří MAYER, R. KRALOVICS, Šárka POSPÍŠILOVÁ and Michael DOUBEK. Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status (Low- burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status.). \textit{Leukemia}. London: Nature Publishing Group, 2018, vol.~32, No~2, p.~450-461. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/leu.2017.230.
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