RAS and TP53 can predict survival in adults with T-cell lymphoblastic leukemia treated with hyper-CVAD.
Cancer Med
; 9(3): 849-858, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31804006
ABSTRACT
Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)-negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown to distinguish low- vs high-risk groups in adult T-ALL patients treated using the Berlin-Frankfurt-Münster ALL protocol. However, it is unknown if this molecular classifier can stratify adult T-ALL patients treated with hyper-CVAD ± nelarabine. We identified a relatively small cohort of 27 adults with T-ALL who were uniformly treated with hyper-CVAD ± nelarabine with available mutational analysis at time of diagnosis. The most commonly mutated genes in this group were NOTCH1 (52%), NRAS (22%), DNMT3A (19%), KRAS (15%), and TP53 (7%). The NFRP molecular classifier failed to stratify overall survival (OS; P = .84) and relapse-free survival (RFS; P = .18) in this cohort. We developed a new stratification model combining K/NRAS and TP53 mutations as high-risk factors and showed that mutations in these genes predicted poorer OS (P = .03) and RFS (P = .04). While the current study is limited by cohort size, these data suggest that the NFRP molecular classifier might not be applicable to adult T-ALL patients treated with hyper-CVAD ± nelarabine. RAS/TP53 mutation status, however, was useful in risk stratification in adults with T-ALL.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Proteína Supressora de Tumor p53
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Proteínas Proto-Oncogênicas p21(ras)
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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GTP Fosfo-Hidrolases
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Proteínas de Membrana
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Recidiva Local de Neoplasia
Tipo de estudo:
Etiology_studies
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Evaluation_studies
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Guideline
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos