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E.-J. Choi et al.
Table 1. Patients’ characteristics at diagnosis.
Characteristic
Sex, n(%) Male
Female
Median age (range), years ICUS, n(%)
CCUS*
Non-CCUS
WHO classification MDS, n(%)
MDS with SLD/RS-SLD MDS with MLD/RS-MLD MDS with EB-1
MDS with EB-2
MDS, unclassifiable
MDS with isolated del(5q) Unknown
AML, n(%)
AML with RGA AML with MRC Therapy-related AML, NOS MPAL
Risk stratification, n(%) MDS
IPSS-R score ≤ 3.5
IPSS-R score > 3.5 AML#
Favorable Intermediate Adverse Unknown
Karyotype, n(%)
Normal
Abnormal
Total (n = 457)
272 (59.5) 185 (40.5) 59 (16-89)
ICUS (n = 75)
37 (49.3)
38 (50.7) 54 (19-89)
42 (56.0) 33 (44.0)
MDS (n = 210)
134 (63.8) 76 (36.2) 61 (18-87)
41 (19.5) 73 (34.8) 45 (21.4) 18 (8.6) 26 (12.4) 2 (1.0)
2 (1.0)
75 (35.7) 135 (64.3)
92 (43.8) 118 (56.2)
AML (n = 172)
101 (58.7) 71 (41.3) 57 (16-81)
230 (50.3)
227 (49.7)
69 (92.0) 6 (8.0)
84 (48.8) 40 (23.3) 7 (4.1) 40 (23.3) 1 (0.6)
63 (36.6) 35 (20.3) 73 (42.4) 1 (0.6)
69 (40.1) 103 (59.9)
ICUS: idiopathic cytopenia of undetermined significance; CCUS: clonal cytopenia of undetermined significance; WHO: World Health Organization; MDS: myelodysplastic syn- drome; SLD: single lineage dysplasia; RS: ring sideroblasts; MLD: multilineage dysplasia; EB: excess blasts; AML: acute myeloid leukemia; RGA: recurrent genetic abnormalities; MRC: myelodysplasia-related changes; NOS, not otherwise specified; MPAL, mixed phenotype acute leukemia; IPSS-R, International Prognostic Scoring System-Revised. *CCUS was defined as ICUS with myeloid neoplasm-related somatic mutations of variant allele frequency ≥2%, or clonal karyotypic abnormalities. #Risk stratification of AML according to the 2017 European LeukemiaNet risk stratification.
(univariate analysis). The Kaplan-Meier survival curves were ren- dered as a graph using Prism version 5.0 (GraphPad Software, Inc., La Jolla, CA, USA). In all analyses, the P-values were two-tailed and those <0.05 were considered statistically significant.
Results
Patients’ characteristics
The clinical characteristics of the 457 included patients at diagnosis are shown in Table 1. There were 75 patients (16%) with ICUS, 210 (46%) with MDS and 172 (38% with AML. The median age at diagnosis was 59 years (range, 16-89), and 60% were men. Forty-two (56.0%) of the ICUS patients had clonal cytopenia of undetermined significance. Disease risk of the MDS patients was lower-
risk in 75 (35.7%) and higher-risk in 135 (64.3%) accord- ing to the Revised International Prognostic Scoring System (IPSS-R).20 Of the AML patients, 63 (36.6%), 35 (20.3%), and 73 (42.4%) were classified into favorable, intermedi- ate, and adverse genetic risk categories, respectively, according to the 2017 European LeukemiaNet risk stratifi- cation.21
Frequency and genetic characteristics of DDX41 mutations
We detected genetic DDX41 mutations in 39 (8.5%) patients. Thirty-four (7.4%) patients had germline muta- tions, of whom 27 (79.4%) also had somatic mutations at the other position of DDX41. Five (1.1%) patients had somatic DDX41 mutations only. In 28 patients, the germline DDX41 mutations were considered causal and
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