OBJECTIVES: Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized. METHODS: 176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype. RESULTS: Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS. TP53 mutations often occurred in DNA-binding domains and the majority of cases had only one mutation, irrespective of their karyotype and MDS subtype. The variant allele frequency (VAF), however, was associated with karyotype complexity and the types of MDS with a lower VAF found in cases with a non-complex karyotype and low-grade MDS. A low (<20%) VAF was associated with a better survival, as well as low-grade subtype. CONCLUSIONS: In low-grade MDS and MDS with a non-complex karyotype, TP53 mutations showed a lower VAF. Patients with a lower VAF had a better survival. TP53 mutations are not the only prognostic factor in MDS patients with TP53 mutations as the VAF, blast counts and history of prior therapy also play important roles in prognosis.
OBJECTIVES: Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized. METHODS: 176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype. RESULTS: Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS. TP53 mutations often occurred in DNA-binding domains and the majority of cases had only one mutation, irrespective of their karyotype and MDS subtype. The variant allele frequency (VAF), however, was associated with karyotype complexity and the types of MDS with a lower VAF found in cases with a non-complex karyotype and low-grade MDS. A low (<20%) VAF was associated with a better survival, as well as low-grade subtype. CONCLUSIONS: In low-grade MDS and MDS with a non-complex karyotype, TP53 mutations showed a lower VAF. Patients with a lower VAF had a better survival. TP53 mutations are not the only prognostic factor in MDSpatients with TP53 mutations as the VAF, blast counts and history of prior therapy also play important roles in prognosis.
Authors: Guillermo Montalban-Bravo; Rashmi Kanagal-Shamanna; Christopher B Benton; Caleb A Class; Kelly S Chien; Koji Sasaki; Kiran Naqvi; Yesid Alvarado; Tapan M Kadia; Farhad Ravandi; Naval Daver; Koichi Takahashi; Elias Jabbour; Gautham Borthakur; Naveen Pemmaraju; Marina Konopleva; Kelly A Soltysiak; Sherry R Pierce; Carlos E Bueso-Ramos; Keyur P Patel; Hagop Kantarjian; Guillermo Garcia-Manero Journal: Blood Adv Date: 2020-02-11
Authors: Detlef Haase; Kristen E Stevenson; Donna Neuberg; Jaroslaw P Maciejewski; Aziz Nazha; Mikkael A Sekeres; Benjamin L Ebert; Guillermo Garcia-Manero; Claudia Haferlach; Torsten Haferlach; Wolfgang Kern; Seishi Ogawa; Yasunobu Nagata; Kenichi Yoshida; Timothy A Graubert; Matthew J Walter; Alan F List; Rami S Komrokji; Eric Padron; David Sallman; Elli Papaemmanuil; Peter J Campbell; Michael R Savona; Adam Seegmiller; Lionel Adès; Pierre Fenaux; Lee-Yung Shih; David Bowen; Michael J Groves; Sudhir Tauro; Michaela Fontenay; Olivier Kosmider; Michal Bar-Natan; David Steensma; Richard Stone; Michael Heuser; Felicitas Thol; Mario Cazzola; Luca Malcovati; Aly Karsan; Christina Ganster; Eva Hellström-Lindberg; Jacqueline Boultwood; Andrea Pellagatti; Valeria Santini; Lynn Quek; Paresh Vyas; Heinz Tüchler; Peter L Greenberg; Rafael Bejar Journal: Leukemia Date: 2019-01-11 Impact factor: 12.883
Authors: Mariko Yabe; Aidana Z Omarbekova; Meier Hsu; Hannah May; Maria E Arcila; Ying Liu; Ahmet Dogan; Andrew M Brunner; Valentina Nardi; Robert P Hasserjian; Virginia M Klimek Journal: Cancers (Basel) Date: 2021-11-02 Impact factor: 6.639