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2 results on '"Yamato G"'

1. Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia.

Author

Yamato G, Yamaguchi H, Handa H, Shiba N, Kawamura M, Wakita S, Inokuchi K, Hara Y, Ohki K, Okubo J, Park MJ, Sotomatsu M, Arakawa H, and Hayashi Y

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, DNA (Cytosine-5-)-Methyltransferases genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methyltransferase 3A, DNA-Binding Proteins metabolism, Female, Histone-Lysine N-Methyltransferase genetics, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Mutation, Myeloid-Lymphoid Leukemia Protein genetics, Nuclear Proteins genetics, Nuclear Proteins metabolism, Nucleophosmin, Transcription Factors metabolism, fms-Like Tyrosine Kinase 3 genetics, Biomarkers, Tumor genetics, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Transcription Factors genetics
Abstract

High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0.010). High PRDM16 expression significantly correlated with DNMT3A (43% vs. 15%, P < 0.001) and NPM1 (43% vs. 21%, P = 0.010) mutations and partial tandem duplication of KMT2A (22% vs. 1%, P < 0.001). Remarkably, high-PRDM16-expression patients were frequent in the noncomplete remission group (48% vs. 21%, P = 0.002). Overall survival (OS) was significantly worse in high-PRDM16-expression patients than in low-PRDM16-expression patients (5-year OS, 18% vs. 34%; P = 0.002). This trend was observed more clearly among patients aged <65 years (5-year OS, 21% vs. 50%; P = 0.001), particularly in FLT3-ITD-negative patients in the intermediate cytogenetic risk group (5-year OS, 25% vs. 59%; P = 0.009). These results suggest that high PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients, similar to pediatric AML patients., (© 2017 Wiley Periodicals, Inc.)

Published
2017
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2. High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial.

Author

Shiba N, Ohki K, Kobayashi T, Hara Y, Yamato G, Tanoshima R, Ichikawa H, Tomizawa D, Park MJ, Shimada A, Sotomatsu M, Arakawa H, Horibe K, Adachi S, Taga T, Tawa A, and Hayashi Y

Subjects
Adolescent, Child, Child, Preschool, Female, Gene Expression genetics, Histone-Lysine N-Methyltransferase genetics, Humans, Infant, Infant, Newborn, Japan epidemiology, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Mutation genetics, Myeloid-Lymphoid Leukemia Protein genetics, Nuclear Pore Complex Proteins genetics, Nucleophosmin, Prognosis, fms-Like Tyrosine Kinase 3 genetics, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Neoplasm Proteins genetics, Transcription Factors genetics
Abstract

Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P < 0·001; NUP98-NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event-free survival (EFS) among PRDM16-overexpressing patients were significantly worse than in patients with low PRDM16 expression (3-year OS: 51% vs. 81%, P < 0·001, 3-year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3-internal tandem duplication-positive AML patients (3-year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate-risk cytogenetic profiles and was independently associated with an adverse outcome., (© 2015 John Wiley & Sons Ltd.)

Published
2016
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