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1. Author Correction: Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author

Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, Yoshizato T, Shiozawa Y, Saiki R, Malcovati L, Levine MF, Arango JE, Zhou Y, Solé F, Cargo CA, Haase D, Creignou M, Germing U, Zhang Y, Gundem G, Sarian A, van de Loosdrecht AA, Jädersten M, Tobiasson M, Kosmider O, Follo MY, Thol F, Pinheiro RF, Santini V, Kotsianidis I, Boultwood J, Santos FPS, Schanz J, Kasahara S, Ishikawa T, Tsurumi H, Takaori-Kondo A, Kiguchi T, Polprasert C, Bennett JM, Klimek VM, Savona MR, Belickova M, Ganster C, Palomo L, Sanz G, Ades L, Della Porta MG, Smith AG, Werner Y, Patel M, Viale A, Vanness K, Neuberg DS, Stevenson KE, Menghrajani K, Bolton KL, Fenaux P, Pellagatti A, Platzbecker U, Heuser M, Valent P, Chiba S, Miyazaki Y, Finelli C, Voso MT, Shih LY, Fontenay M, Jansen JH, Cervera J, Atsuta Y, Gattermann N, Ebert BL, Bejar R, Greenberg PL, Cazzola M, Hellström-Lindberg E, Ogawa S, and Papaemmanuil E

Published
2021

2. Implications ofTP53allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author

Bernard, E, Nannya, Y, Hasserjian, RP, Devlin, SM, Tuechler, H, Medina-Martinez, JS, Yoshizato, T, Shiozawa, Y, Saiki, R, Malcovati, L, Levine, MF, Arango, JE, Zhou, YY, Sole, F, Cargo, CA, Haase, D, Creignou, M, Germing, U, Zhang, YM, Gundem, G, Sarian, A, van de Loosdrecht, AA, Jadersten, M, Tobiasson, M, Kosmider, O, Follo, MY, Thol, F, Pinheiro, RF, Santini, V, Kotsianidis, I, Boultwood, J, Santos, FPS, Schanz, J, Kasahara, S, Ishikawa, T, Tsurumi, H, Takaori-Kondo, A, Kiguchi, T, Polprasert, C, Bennett, JM, Klimek, VM, Savona, MR, Belickova, M, Ganster, C, Palomo, L, SANZ, G, Ades, L, Della Porta, MG, Smith, AG, Werner, Y, Patel, M, Viale, A, Vanness, K, Neuberg, DS, Stevenson, KE, Menghrajani, K, Bolton, KL, Fenaux, P, Pellagatti, A, Platzbecker, U, Heuser, M, Valent, P, Chiba, S, Miyazaki, Y, Finelli, C, Voso, MT, Shih, LY, Fontenay, M, Jansen, JH, Cervera, J, Atsuta, Y, Gattermann, N, Ebert, BL, Bejar, R, Greenberg, PL, Cazzola, M, Hellstrom-Lindberg, E, Ogawa, S, and Papaemmanuil, E

Abstract

Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states ofTP53and clinical presentation Tumor protein p53 (TP53) is the most frequently mutated gene in cancer(1,2). In patients with myelodysplastic syndromes (MDS),TP53mutations are associated with high-risk disease(3,4), rapid transformation to acute myeloid leukemia (AML)(5), resistance to conventional therapies(6-8)and dismal outcomes(9). Consistent with the tumor-suppressive role ofTP53, patients harbor both mono- and biallelic mutations(10). However, the biological and clinical implications ofTP53allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS forTP53mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third ofTP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only.TP53multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)(11). Surprisingly, monoallelic patients did not differ fromTP53wild-type patients in outcomes and response to therapy. This study shows that consideration ofTP53allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response.

Published
2020

3. Prolonged survival in patients >= 60 years with first relapsed/refractory acute myeloid leukemia treated with vosaroxin plus cytarabine vs placebo plus cytarabine: Results from the phase 3 VALOR study

Author

Krug, U, Ravandi, F, Ritchie, EK, Sayar, H, Lancet, JE, Craig, MD, Vey, N, Strickland, SA, Schiller, GJ, Jabbour, E, Erba, HP, Pigneux, A, Horst, H-A, Recher, C, Klimek, VM, Cortes, J, Roboz, GJ, Craig, AR, Fox, JA, Ward, R, Smith, JA, Acton, G, Mehta, C, Kantarjian, HM, and Stuart, RK

Published
2015

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