Clinicopathologic and genetic characterization of nonacute NPM1-mutated myeloid neoplasms Journal Article


Authors: Patel, S. S.; Ho, C.; Ptashkin, R. N.; Sadigh, S.; Bagg, A.; Geyer, J. T.; Xu, M. L.; Prebet, T.; Mason, E. F.; Seegmiller, A. C.; Morgan, E. A.; Steensma, D. P.; Winer, E. S.; Wong, W. J.; Hasserjian, R. P.; Weinberg, O. K.
Article Title: Clinicopathologic and genetic characterization of nonacute NPM1-mutated myeloid neoplasms
Abstract: NPM1-mutated myeloid neoplasms (NPM1+ MNs) with <20% blood or bone marrow blasts are rare and have been previously shown in limited case series to exhibit an aggressive clinical course. We assembled the largest cohort of NPM1+ MN cases to date (n = 45) and compared it with NPM1- MN (n = 95) and NPM1+ de novo acute myeloid leukemia (AML; n = 119) patients. Compared with NPM1- MN, NPM1+ MN were associated with younger age (P = .007), a normal karyotype (P < .0001), more frequent mutations involving DNMT3A (P = .01) and PTPN11 (P = .03), and fewer involving ASXL1 (P = .003), RUNX1 (P = .0004), and TP53 (P = .02). Mutations involving IDH1 or IDH2 (IDH1/2) (P = .007) and FLT3 (internal tandem duplication, P < .0001; noninternal tandem duplication, P = .01) were less frequent in NPM1+ MN than in NPM1+ AML. In multivariable analyses performed in patients with myelodysplastic syndrome only, total mutation count (hazard ratio [HR], 1.3; P = .05), NPM1 mutation (HR, 3.6; P = .02), TP53 mutation (HR, 5.2; P = .01), and higher International Prognostic Scoring System-R score (HR, 1.7; P = .0003) were independently associated with shorter overall survival, whereas stem cell transplant conferred a favorable effect (HR, 0.1; P < .0001). These data suggest that NPM1+ MN are biologically distinct from NPM1- MN. Similar to NPM1+ AML, patients with NPM1-mutated myelodysplastic syndrome may benefit from more intensive therapeutic regimens. © 2019 by The American Society of Hematology.
Keywords: signal transduction; adult; cancer survival; controlled study; aged; gene mutation; major clinical study; overall survival; sequence analysis; clinical feature; comparative study; genetic analysis; disease association; cohort analysis; cytogenetics; protein p53; myelodysplastic syndrome; immunophenotyping; karyotype; protein tyrosine phosphatase shp 2; transcription factor runx1; dna methyltransferase 3a; myeloid leukemia; asxl1 gene; cd135 antigen; nucleophosmin; clinical outcome; acute myeloid leukemia; tp53 gene; dnmt3a gene; npm1 gene; international prognostic scoring system; human; male; female; priority journal; article; runx1 gene; ptpn11 gene
Journal Title: Blood Advances
Volume: 3
Issue: 9
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2019-05-14
Start Page: 1540
End Page: 1545
Language: English
DOI: 10.1182/bloodadvances.2019000090
PUBMED: 31085507
PROVIDER: scopus
PMCID: PMC6517660
DOI/URL:
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
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  1. Caleb   Ho
    27 Ho