High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML

Publication Date:
2018-06-22
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Myeloid Neoplasia, Clinical Trials and Observations
Published by:
http://www.hematology.org/
_version_ 1836398981210439680
autor Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
beschreibung Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3 ) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P 〈 .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P 〈 .0001) compared with the other NPM1 -mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission ( P = .0004) and in patients with mutated DNMT3A ( P 〈 .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
citation_standardnr 6289600
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-06-22
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/25/2816?rss=1
schlagwort Myeloid Neoplasia, Clinical Trials and Observations
search_space articles
shingle_author_1 Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
shingle_author_2 Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
shingle_author_3 Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
shingle_author_4 Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
shingle_catch_all_1 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
Myeloid Neoplasia, Clinical Trials and Observations
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3 ) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1 -mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission ( P = .0004) and in patients with mutated DNMT3A ( P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
Myeloid Neoplasia, Clinical Trials and Observations
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3 ) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1 -mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission ( P = .0004) and in patients with mutated DNMT3A ( P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
Myeloid Neoplasia, Clinical Trials and Observations
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3 ) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1 -mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission ( P = .0004) and in patients with mutated DNMT3A ( P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
Myeloid Neoplasia, Clinical Trials and Observations
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3 ) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1 -mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission ( P = .0004) and in patients with mutated DNMT3A ( P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
Patel, S. S., Kuo, F. C., Gibson, C. J., Steensma, D. P., Soiffer, R. J., Alyea, E. P., Chen, Y.-B. A., Fathi, A. T., Graubert, T. A., Brunner, A. M., Wadleigh, M., Stone, R. M., De; Angelo, D. J., Nardi, V., Hasserjian, R. P., Weinberg, O. K.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
shingle_title_2 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
shingle_title_3 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
shingle_title_4 High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
timestamp 2025-06-30T23:35:42.902Z
titel High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
titel_suche High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML
topic W
WW-YZ
uid ipn_articles_6289600