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Blood Adv. 2019 May 14;3(9):1540-1545. doi: 10.1182/bloodadvances.2019000090.

Clinicopathologic and genetic characterization of nonacute NPM1-mutated myeloid neoplasms.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
2
Division of Hematopathology, Memorial Sloan Kettering Cancer Center, New York, NY.
3
Division of Hematopathology, Department of Pathology, Hospital of the University of Pennsylvania and Perelman School of Medicine, Philadelphia, PA.
4
Division of Hematopathology, Weill Cornell Medical College, New York, NY.
5
Department of Pathology and Laboratory Medicine and.
6
Division of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
7
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN.
8
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
9
Department of Pathology, Massachusetts General Hospital, Boston, MA; and.
10
Department of Pathology, Boston Children's Hospital, Boston, MA.

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.

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