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Article

Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1

by
Min-Seung Park
1,
Dae-Ho Choi
2,
Jun Ho Jang
2,
Chul Won Jung
2,
Hee-Jin Kim
3 and
Hyun-Young Kim
3,*
1
Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
2
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
3
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(19), 7074; https://doi.org/10.3390/jcm14197074
Submission received: 13 September 2025 / Revised: 26 September 2025 / Accepted: 4 October 2025 / Published: 7 October 2025
(This article belongs to the Section Hematology)
Browse Figures
Versions Notes

Abstract

Background: Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are rare hematopoietic disorders that exhibit overlapping pathological and molecular features of both MDS and MPN. This study aimed to investigate the mutational profiles and prognostic implications of MDS/MPN subtypes in Korean patients. Methods: We retrospectively reviewed 53 patients with MDS/MPN who underwent bone marrow examination and next-generation sequencing panel testing. Overall survival was analyzed with 3-year censoring. The cohort included chronic myelomonocytic leukemia (CMML; N = 30); MDS/MPN with neutrophilia (N = 6); MDS/MPN with SF3B1 mutation and thrombocytosis (N = 4); and MDS/MPN, not otherwise specified (MDS/MPN-NOS; N = 13). Results: The most frequently mutated gene was ASXL1 (52.8%), followed by TET2 (39.6%) and U2AF1 (18.9%), in total MDS/MPN. U2AF1 mutations were particularly frequent in myelodysplastic CMML (33.3%) and MDS/MPN-NOS (30.8%). In CMML, ASXL1 and TET2 mutations were associated with a trend toward better prognosis compared with wild-type (HR 0.21, p = 0.052; HR 0.25, p = 0.057, respectively), while U2AF1 mutations were associated with adverse prognosis in univariate analysis with borderline significance (HR 12.20, p = 0.050). Clinical/Molecular CMML-Specific Prognostic Scoring System and Mayo Molecular Model showed stepwise survival patterns across risk groups without statistical significance. In univariate analysis, transfusion dependency was associated with poor prognosis (HR 7.78, p = 0.013). Conclusions: This study provides the first single-institution analysis in Korean patients with MDS/MPN and identified U2AF1 mutations as a potentially significant prognostic factor, enhancing the molecular understanding of MDS/MPN.

1. Introduction

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a rare group of clonal hematopoietic disorders that exhibit overlapping pathologic and molecular features of both MDS and MPN [1,2]. The World Health Organization (WHO) 5th edition classification recognizes four distinct subtypes within this category: chronic myelomonocytic leukemia (CMML); MDS/MPN with neutrophilia (MDS/MPN-N); MDS/MPN with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T); and MDS/MPN, not otherwise specified (MDS/MPN-NOS) [3]. While these entities share the common characteristic of combined cytopenias and proliferative features on peripheral blood, they can be distinguished by specific hematologic and molecular criteria. CMML is defined by persistent peripheral blood monocytosis (absolute count ≥ 0.5 × 109/L and relative count ≥ 10% of white blood cells [WBCs]), with additional diagnostic requirements varying based on the absolute monocyte count; MDS/MPN-N is characterized by neutrophilia with dysplasia and ≥ 10% circulating immature myeloid cells; and MDS/MPN-SF3B1-T presents with thrombocytosis in conjunction with SF3B1 mutation and associated dyserythropoiesis, frequently manifesting with ring sideroblasts [4].
CMML, the most common subtype among MDS/MPNs, is further subclassified based on WBC count into myelodysplastic CMML (MD-CMML, WBC count < 13 × 109/L) and myeloproliferative CMML (MP-CMML, WBC count ≥ 13 × 109/L) [5]. These subtypes demonstrate distinct clinicopathological characteristics with differences in mutational distribution and prognosis [6]. The molecular landscape of CMML is characterized by recurrent mutations affecting three major pathways: epigenetic regulation of transcription and histone modification (e.g., TET2 and ASXL1), RNA splicing factors (e.g., SRSF2, U2AF1, and SF3B1), and signal transduction pathways (e.g., KRAS, NRAS, and CBL) [5]. Notably, mutations in epigenetic and splicing genes are more frequently associated with MD-CMML, while alterations in cellular signaling pathways show stronger association with MP-CMML [7]. U2AF1 mutations occur predominantly at two hotspots (S34 and Q157) with distinct biological effects, particularly S34 mutations showing growth-inhibitory properties that may contribute to their enrichment in the more dysplastic subtype [8,9]. MDS/MPN-N and MDS/MPN-SF3B1-T share similar overall mutational profiles with CMML, though specific mutations show strong disease associations: SETBP1 and ETNK1 mutations are particularly enriched in MDS/MPN-N, while SF3B1 mutations are, by definition, strongly associated with MDS/MPN-SF3B1-T [10,11].
Risk assessment in MDS/MPN has been most extensively studied in CMML, with several prognostic scoring systems proposed [6]. Among these, the Clinical/Molecular CMML-Specific Prognostic Scoring System (CPSS-Mol) and the Mayo Molecular Model (MMM) have gained widespread acceptance [6]. The CPSS-Mol incorporates clinical parameters including red blood cell (RBC) transfusion dependency, WBC count, hemoglobin (Hb) level, platelet count, bone marrow (BM) blast percentage, and cytogenetic risk groups, along with molecular markers such as ASXL1, NRAS, RUNX1, and SETBP1 mutations [12]. In contrast, the MMM provides a more streamlined approach, excluding RBC transfusion dependency and cytogenetic abnormalities while incorporating only ASXL1 mutation status among molecular markers, alongside absolute monocyte count, Hb level, platelet count, and presence of circulating immature myeloid cells [13].
Given the rarity of MDS/MPNs and the recent adoption of next-generation sequencing (NGS)-based multigene panel testing in clinical practice, data on the molecular profiles of these disorders in Korean patients remain limited. This study aimed to comprehensively characterize the mutational landscape of MDS/MPN subtypes in Korean patients and to assess the applicability of molecular-based prognostic systems.

2. Materials and Methods

2.1. Study Participants

We retrospectively reviewed 53 patients diagnosed with MDS/MPN who underwent NGS gene panel testing between March 2019 and June 2025, including 15 patients with MD-CMML (WBC count < 13 × 109/L; 14 with CMML-1 and one with CMML-2), 15 with MP-CMML (WBC count ≥ 13 × 109/L; 12 with CMML-1 and 3 with CMML-2), 6 with MDS/MPN-N, 4 with MDS/MPN-SF3B1-T, and 13 with MDS/MPN-NOS. All BM diagnoses were re-evaluated according to the WHO 5th edition classification criteria [3], and diagnoses were revised when necessary. Clinical and laboratory data were collected from electronic medical records, including sex, age, complete blood cell count, BM examination results, conventional cytogenetics, fluorescence in situ hybridization (FISH), presence of splenomegaly, RBC transfusion dependency at diagnosis (defined as requiring at least one unit of RBC every 8 weeks over a 16 weeks period) [14], and treatment regimens. This study was approved by the Institutional Review Board of Samsung Medical Center with a waiver of informed consent (SMC 2025-08-126).

2.2. Next-Generation Sequencing for Myeloid Neoplasm-Related Genes

Genomic DNA was extracted from BM aspirates or peripheral blood samples using the Wizard Genomic DNA Purification Kit (Promega, Madison, WI, USA). Library preparation was conducted using IDT xGen pre-designed/custom probes (Integrated DNA Technologies, Coralville, IA, USA). Following library preparation, targeted sequencing was performed on the NextSeq 550Dx platform (Illumina, San Diego, CA, USA). The sequencing panel included 37 myeloid neoplasm-associated genes (ABL1, ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PRPF8, PTPN11, RB1, RUNX1, SETBP1, SF3B1, SH2B3, SRSF2, STAG2, TET2, TP53, U2AF1, WT1, and ZRSR2) [15,16,17]. Sequencing reads were aligned to the GRCh37/hg19 reference using BWA-MEM, processed with Picard, and variants were called with GATK (HaplotypeCaller, Mutect2), Pisces, and Pindel. Variants were filtered with custom quality control scripts and annotated using snpEff with population databases. Target coverage depth was 1000×, with variant calling performed using threshold of ≥2.0% variant allele frequency (VAF) or ≥20 supporting reads. NGS analysis was performed using tumor samples only, without matched normal tissue samples. Identified variants were interpreted according to the 2017 AMP/ASCO/CAP somatic tier guidelines and 2022 ClinGen/CGC/VICC oncogenicity guidelines [18,19], and (likely) oncogenic variants classified as tier 1 or 2 were included in this study.

2.3. Statistical Analysis

Overall survival (OS) was defined as the time from initial diagnosis to death from any cause or last follow-up, with patients censored at 3 years for analysis due to heterogeneity in follow-up duration. Kaplan–Meier curves with log-rank tests were used to compare survival between MDS/MPN subtypes and validate risk stratification (CPSS-Mol and MMM scoring systems) [12,13]. The discriminatory ability of prognostic scoring systems was assessed using concordance index (C-index) with 95% confidence intervals (CIs). For evaluation of individual prognostic factors, univariate Cox proportional regression was performed to calculate hazard ratios (HRs) and 95% CIs. For multivariate analysis, a pre-specified model including age, CMML subtype (MD vs. MP), high-risk cytogenetics, and mutational status of ASXL1 and U2AF1 was analyzed using Firth-penalized Cox regression due to the limited number of events. All statistical analyses and data visualization were performed using R software version 4.5.1 (R Foundation for Statistical Computing, Vienna, Austria), and a p-value < 0.05 was considered statistically significant.

3. Results

3.1. Patients’ Characteristics

Clinical and laboratory characteristics of the 53 patients with MDS/MPN and their subtypes are summarized in Table 1. The cohort was predominantly male (69.8%) with a median age of 68 years (range, 37–87). At diagnosis, median WBC count was 18.57 × 109/L (range, 2.97–136.82), Hb 8.2 g/dL (5.4–15.5), and platelet count 107 × 109/L (6–1343). Morphologic dysplasia was most frequently observed in the megakaryocytic lineage (84.9%), followed by granulocytic (75.5%) and erythroid lineages (54.7%). Grade 2 or higher myelofibrosis was present in 26.4% of patients. Cytogenetic analysis, including conventional karyotyping and FISH, revealed monosomy 7/del(7q) and trisomy 8 as the most frequent abnormalities, each occurring in 11.3% of patients. Patients harbored a median of 3 mutated genes (range, 0–7), and ASXL1 and TET2 co-mutations were observed in 22.6%. Splenomegaly was observed in 17.0% of patients at diagnosis. RBC transfusion dependency was present in 37.7% of patients at initial diagnosis, and 9.4% underwent allogeneic hematopoietic stem cell transplantation during the follow-up period. Disease progression or relapse within 3 years of diagnosis occurred in 15.1% of patients, and 26.4% died during a median follow-up of 1.16 years (interquartile range, 0.19–2.85 years; reverse Kaplan–Meier method).

3.2. Mutational Landscape Across MDS/MPN Subtypes

ASXL1 and TET2 were the most frequently mutated genes across MDS/MPN subtypes, with distinct patterns in each subtype (Figure 1A and Supplemental Table S1). Overall, ASXL1 mutations occurred in 52.8% of patients, followed by TET2 (39.6%), U2AF1 (18.9%), KRAS (17.0%), SF3B1 (17.0%), and NRAS (15.1%). In MD-CMML, ASXL1 and TET2 mutations were the most common (40.0% each), followed by U2AF1 (33.3%), KRAS, NF1, and SRSF2 (20.0% each). In MP-CMML, ASXL1 and TET2 mutations were also the most common (60.0% each), followed by NRAS (33.3%), EZH2, and KRAS (26.7% each), while SRSF2 mutations were relatively rare (6.7%). In MDS/MPN-N, ASXL1 (66.7%) and TET2 (50.0%) mutations were the most frequent, followed by CBL, CSF3R, and SETBP1 (33.3% each). Patients with MDS/MPN-SF3B1-T uniformly harbored SF3B1 mutations (100%) and frequently exhibited JAK2 mutations (50.0%). In MDS/MPN-NOS, ASXL1 was the most prevalent (69.2%), followed by SETBP1 and U2AF1 (30.8% each). Detailed oncoprint visualization by disease subtype is presented in Figure 1B.
Among U2AF1 mutations (N = 10), S34 hotspot mutations were predominant (60.0%), including S34F (N = 5) and S34Y (N = 1), while Q157P mutations occurred in 4 patients (40.0%) (Supplemental Figure S1). The VAFs ranged from 9.8% to 52.3% (median, 34.0%). U2AF1 mutations showed differential distribution across subtypes, being more frequent in MD-CMML (5/15, 33.3%) compared to MP-CMML (1/15, 6.7%), with S34 mutations predominating in MD-CMML (4/5, 80.0%).

3.3. Survival and Prognostic Factors in the MDS/MPN Cohort

3.3.1. Survival Analysis by MDS/MPN Subtypes

No significant survival differences were observed across MDS/MPN subtypes (p = 0.360) (Figure 2), likely due to small sample sizes and limited follow-up. Estimated OS probabilities at the last follow-up within 3 years were 50.8% for MD-CMML (3.0 years; 95% CI: 23.9–100%), 21.6% for MP-CMML (2.85 years; 95% CI: 4.0–100%), 66.7% for MDS/MPN-N (3.0 years; 95% CI: 30.0–100%), 100% for MDS/MPN-SF3B1-T (3.0 years; 95% CI: not estimable), and 52.5% for MDS/MPN-NOS (3.0 years; 95% CI: 27.2–100%). Although MP-CMML showed a trend toward inferior survival, pairwise comparisons between subtypes did not reach statistical significance (all p > 0.05).

3.3.2. Prognostic Impact of Gene Mutations in MDS/MPN

Mutations in ASXL1, TET2, and U2AF1 showed varying prognostic trends in the overall MDS/MPN cohort. Patients with ASXL1 and TET2 wild-type showed a trend toward inferior OS compared to those with mutations, while U2AF1 mutations showed a trend toward adverse prognosis (Figure 3A–C). However, these trends did not reach statistical significance (all p > 0.05).

3.4. Survival and Prognostic Factors in CMML

3.4.1. Prognostic Impact of Gene Mutations

In CMML patients, U2AF1 mutations showed borderline significance with worse survival (HR 12.2, 95% CI: 1.0–148.1, p = 0.050), while ASXL1 and TET2 mutations showed favorable trends (p = 0.052 and p = 0.057, respectively) (Figure 3D–F).

3.4.2. Survival Analysis by Prognostic Scoring Systems

Survival in CMML patients varied by prognostic scoring systems, though differences were not statistically significant (Figure 4). Using CPSS-Mol, OS estimates at the last follow-up within 3 years were 100% for low risk (0.97 years; 95% CI not estimable), 60.0% for intermediate-1 (3.0 years; 95% CI 29.3–100%), 35.7% for intermediate-2 (2.85 years; 95% CI 8.3–100%), and 0% for high risk (2.21 years; 95% CI not estimable). By MMM categories, OS estimates were 50.0% for intermediate-1 (2.85 years; 95% CI 12.5–100%), 37.5% for intermediate-2 (1.67 years; 95% CI 13.0–100%), and 20.0% for high risk (3.0 years; 95% CI 3.5–100%). Higher-risk groups showed trends toward inferior survival, but differences were not statistically significant (p = 0.590 for CPSS-Mol and p = 0.061 for MMM; all pairwise p > 0.05). The C- index was 0.510 (95% CI: 0.039–0.981) for CPSS-Mol and 0.466 (95% CI: 0.105–0.828) for MMM.

3.4.3. Clinical and Molecular Prognostic Variables

Univariate Cox regression identified transfusion dependency as a significant adverse prognostic factor for OS in CMML (HR 7.78, 95% CI: 1.55–39.23, p = 0.013) (Supplemental Table S2 and Figure S2). Low platelet count, high-risk cytogenetics, absence of ASXL1 mutation, and presence of U2AF1 mutation showed borderline associations with poor prognosis, but none retained independent significance in multivariate analysis.

4. Discussion

Given the clinical and biological heterogeneity of MDS/MPN, comprehensive molecular characterization is critical to improve prognostication and therapeutic strategies. Accordingly, following the implementation of NGS in routine clinical practice, we conducted a retrospective analysis to characterize the mutational profiles and clinical outcomes of Korean patients with MDS/MPN. However, the single-institution design and limited sample sizes of this study necessitate careful interpretation of subtype-specific findings.
In CMML, ASXL1 and TET2 were the most frequently mutated genes, observed in 40.0% of MD-CMML and 60.0% of MP-CMML patients. These frequencies are consistent with previous studies reporting ASXL1 mutations in 26–45% and TET2 mutations in 46–59% of CMML cases [20,21]. In contrast, U2AF1 mutations were more frequent in our study (20.0% in CMML) compared to the 5–10% typically reported [6,22]. Conversely, SRSF2 mutations were less common (13.3% in CMML) than the 25–47% previously reported [23]. Notably, previous studies in Chinese cohorts have also shown variability, with one reporting a U2AF1 mutation frequency of 4.3% [24] and another reporting 23%, the latter being associated with an absolute monocyte count (AMC) < 1 × 109/L [25]. Similarly, in our study, U2AF1 mutations were more frequent in MD-CMML (33.3%) compared with MP-CMML (6.7%), suggesting that the growth-inhibitory effects of U2AF1 mutations align with the dysplastic phenotype [8]. In our study, both S34 (S34F/S34Y) and Q157P U2AF1 mutations were identified, with S34 being slightly more frequent. The higher U2AF1 mutation frequency in our cohort may reflect ethnic predilection in East Asian populations, while the mutually exclusive relationship between U2AF1 and SRSF2 splicing factor mutations may explain the relatively lower SRSF2 mutation frequency [9].
In MDS/MPN-N, ASXL1 (66.7%) and TET2 (50.0%) were also the most commonly mutated genes, with frequencies at the upper end of the reported ranges of 22–86% and 8–40%, respectively [26]. SETBP1 (33.3%) and CBL (33.3%) were also recurrent. However, ETNK1 mutations (typically 7–16% [26]) were not evaluated as this gene was not included in our sequencing panel. In MDS/MPN-SF3B1-T, SF3B1 was universal (100%), with JAK2 (50.0%) and MPL (25.0%) co-mutations comparable to published frequencies, whereas TET2, DNMT3A, ASXL1 (15–30% in previous studies [11,27]) was absent. Given the small sample sizes of MDS/MPN-N and MDS/MPN-SF3B1-T, these frequencies may not accurately reflect the true distribution, and further studies with larger cohorts will be needed to confirm the overall mutational landscape. In MDS/MPN-NOS, ASXL1 (69.2%), U2AF1 (30.8%), and SETBP1 (30.8%) occurred at higher frequencies than those reported in previous studies (21–55% [28,29], 11–18% [29,30], and 10–12% [29,30], respectively). These findings further support the observation of a relatively higher prevalence of ASXL1 and U2AF1 in Korean patients with MDS/MPN.
In the prognostic analysis by mutational status, statistical significance was not reached, but patients with ASXL1 wild-type showed a trend toward poorer outcomes compared with those harboring ASXL1 mutations. ASXL1 encodes a chromatin regulator and has been consistently associated with adverse prognosis across myeloid neoplasms including AML, MDS, MPN, and MDS/MPN [31]. Our contradictory findings should be interpreted carefully, as they may be attributed to the skewed distribution of enrolled patients, with a large proportion classified into intermediate-2 and high risk groups (73.3% and 76.7% by CPSS-Mol and MMM, respectively), potential cohort bias from our single-institution design, and confounding effects of other concurrent mutations or clinical risk factors. TET2 has been reported to exert a protective effect in CMML [32], and in our study, patients with TET2 mutations demonstrated a tendency toward better outcomes. U2AF1, which is a spliceosome component involved in 3′ splice site recognition and has been associated with poor outcomes in previous studies [33], was the only mutation that reached borderline statistical significance (p = 0.050). Importantly, while the prognostic effect of ASXL1 appeared diminished in advanced risk groups, U2AF1 retained prognostic relevance. Considering the relatively high frequency and potential clinical utility of U2AF1 in East Asian cohorts, our findings suggest that U2AF1 may warrant consideration in future risk stratification models. However, in multivariate analysis, neither U2AF1 mutations nor other variables included in established risk stratification systems achieved statistical significance, which may be attributed to the limited sample size of 30 CMML patients in our cohort. The loss of statistical significance in multivariate models likely reflects insufficient statistical power to detect independent prognostic effects when multiple variables are analyzed simultaneously. Therefore, larger multicenter studies with adequate sample sizes will be essential to validate the independent prognostic value of U2AF1 mutations and to determine their potential incorporation into refined risk stratification models for CMML patients.
In the risk stratification analysis of CMML, both the CPSS-Mol and MMM demonstrated stepwise survival patterns across risk groups, but neither achieved statistical significance. C-index analysis further revealed poor discriminatory ability, with values approaching or below random prediction. The limited discriminatory performance is likely due to the small sample size and the low number of events, which reduced statistical power. Additionally, while these Western-derived scoring systems have demonstrated robust performance in larger international cohorts, their applicability to Korean patients may be influenced by population-specific genetic or clinical factors. These findings underscore the importance of validation in larger Korean cohorts to ascertain whether the observed limitations arise from sample size constraints or reflect true biological differences.
This study has several limitations. First, the small sample sizes in MDS/MPN subtypes other than CMML reduced the statistical power and limited the strength of subtype-specific conclusions. This constraint is further highlighted by unexpected findings such as the contradictory prognostic impact of ASXL1 mutations and the lack of statistical significance in multivariate analysis. Second, our NGS panel did not include some diagnostically important genes such as ETNK1, which is frequently mutated in MDS/MPN-N [11]. Third, the analysis did not account for hematopoietic stem cell transplantation as a time-dependent covariate, which may have affected the survival estimates.
In conclusion, this study represents the first single-institution analysis of mutational and prognostic features in Korean patients with MDS/MPN, providing important insights into the mutational spectrum and its clinical implications. Despite the limitations of sample size, our findings suggest that U2AF1 may play a particularly important role in Korean patients, both in terms of prevalence and prognostic impact. Further validation in larger, multi-institutional East Asian cohorts is essential to confirm the generalizability of these observations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm14197074/s1, Table S1. Distribution of total mutated genes across MDS/MPN subtypes; Table S2. Univariate and multivariate Cox regression analysis for overall survival in patients with CMML; Figure S1. Distribution of variant allele frequencies of U2AF1 mutations in patients with MDS/MPN, stratified by mutation hotspot (S34 vs. Q157); Figure S2. Forest plot of hazard ratios for 3-year overall survival in patients with CMML.

Author Contributions

Conceptualization, H.-Y.K.; Formal analysis, M.-S.P.; Resources, D.-H.C., J.H.J. and C.W.J.; Writing—original draft, M.-S.P.; Writing—review and editing, H.-Y.K.; Supervision, H.-J.K.; Project administration, H.-Y.K., Funding acquisition, H.-Y.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by a grant provided by the National Research Foundation of Korea (NRF), funded by the Korean Government (MSIT) (RS-2025-00519514).

Institutional Review Board Statement

This study was conducted in accordance with the Decla-ration of Helsinki and approved by the Institutional Review Board of Samsung Medical Center (IRB No. 2025-08-126).

Informed Consent Statement

Patient consent was waived due to the retrospective design of the study and the use of de-identified data.

Data Availability Statement

All data relevant to this study have been included in the article or uploaded as Supplementary Information. The additional data presented in this study are available upon request from the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. (A) Distribution of major mutated genes across MDS/MPN subtypes. (B) Oncoprint of genetic mutations in MDS/MPN patients by disease subtype.
Figure 1. (A) Distribution of major mutated genes across MDS/MPN subtypes. (B) Oncoprint of genetic mutations in MDS/MPN patients by disease subtype.
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Figure 2. Kaplan–Meier curves for overall survival by MDS/MPN subtypes. Event counts (deaths/total patients) are as follows: MD-CMML (4/15), MP-CMML (5/15), MDS/MPN-N (1/6), MDS/MPN-SF3B1-T (0/4), and MDS/MPN-NOS (4/13).
Figure 2. Kaplan–Meier curves for overall survival by MDS/MPN subtypes. Event counts (deaths/total patients) are as follows: MD-CMML (4/15), MP-CMML (5/15), MDS/MPN-N (1/6), MDS/MPN-SF3B1-T (0/4), and MDS/MPN-NOS (4/13).
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Figure 3. Kaplan–Meier plots for overall survival according to ASXL1, TET2, and U2AF1 mutations in the entire MDS/MPN cohort ((A–C), N = 53) and the CMML subtype ((D–F), N = 30). In total MDS/MPN cohort (A–C), event counts (deaths/total patients) are ASXL1 wild-type (9/25), ASXL1 mutant (5/28), TET2 wild-type (10/32), TET2 mutant (4/21), U2AF1 wild-type (11/43), and U2AF1 mutant (3/10). In CMML cohort (D–F), ASXL1 wild-type (7/15), ASXL1 mutant (2/15), TET2 wild-type (6/15), TET2 mutant (3/15), U2AF1 wild-type (7/24), and U2AF1 mutant (2/6).
Figure 3. Kaplan–Meier plots for overall survival according to ASXL1, TET2, and U2AF1 mutations in the entire MDS/MPN cohort ((A–C), N = 53) and the CMML subtype ((D–F), N = 30). In total MDS/MPN cohort (A–C), event counts (deaths/total patients) are ASXL1 wild-type (9/25), ASXL1 mutant (5/28), TET2 wild-type (10/32), TET2 mutant (4/21), U2AF1 wild-type (11/43), and U2AF1 mutant (3/10). In CMML cohort (D–F), ASXL1 wild-type (7/15), ASXL1 mutant (2/15), TET2 wild-type (6/15), TET2 mutant (3/15), U2AF1 wild-type (7/24), and U2AF1 mutant (2/6).
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Figure 4. Overall survival of CMML patients stratified by (A) CPSS-Mol and (B) MMM risk categories, and (C) concordance between the two models. Gray-shaded areas indicate identical risk category assignments between CPSS-Mol and MMM.
Figure 4. Overall survival of CMML patients stratified by (A) CPSS-Mol and (B) MMM risk categories, and (C) concordance between the two models. Gray-shaded areas indicate identical risk category assignments between CPSS-Mol and MMM.
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Table 1. Clinical and laboratory characteristics of patients with MDS/MPN.
Table 1. Clinical and laboratory characteristics of patients with MDS/MPN.
Total MDS/MPN
(N = 53)		MD-CMML
(N = 15)		MP-CMML
(N = 15)		MDS/MPN-N
(N = 6)		MDS/MPN-SF3B1-T
(N = 4)		MDS/MPN-NOS
(N = 13)
Demographics
 Male37 (69.8%)10 (66.7%)9 (60.0%)5 (83.3%)3 (75.0%)10 (76.9%)
 Age, years (range)68 (37–87)69 (41–79)68 (37–85)68 (41–85)74 (65–82)65 (40–87)
Laboratory findings
 WBC count (×109/L)18.57 (2.97–136.82)6.94 (2.97–12.14)27.07 (13.98–70.26)40.92 (22.30–136.82)4.80 (3.99–6.41)19.53 (4.03–71.86)
 Hb (g/dL)8.2 (5.4–15.5)8.7 (6.0–15.5)8.1 (5.8–11.2)9.4 (7.1–12.0)8.4 (5.4–9.2)8.1 (6.6–12.1)
 PLT count (×109/L)107 (6–1343) 88 (11–625)93 (6–347)133 (29–480)512 (434–721)107 (11–1343)
 Blast (%)0 (0–8)0 (0–4)1 (0–7)2 (0–3)0 (0–0)1 (0–8)
 Monocyte (×109/L)2.31 (0.20–13.86)2.03 (0.78–3.98)6.38 (2.31–13.86)2.22 (1.34–4.16)0.42 (0.35–0.60)0.63 (0.20–6.47)
Bone marrow findings
 Erythroid dysplasia29 (54.7%)9 (60.0%)8 (53.3%)4 (66.7%)4 (100%)5 (38.5%)
 Granulocytic dysplasia40 (75.5%)12 (80.0%)12 (80.0%)6 (100%)0 (0%)10 (76.9%)
 Megakaryocytic dysplasia45 (84.9%)14 (93.3%)14 (93.3%)6 (100%)2 (50.0%)9 (69.2%)
 Myelofibrosis (grade ≥ 2)14 (26.4%)4 (26.7%)4 (26.7%)1 (16.7%)1 (25.0%)4 (30.8%)
Cytogenetic study
 -7 or del(7q)6 (11.3%)4 (26.7%)1 (6.7%)0 (0%)0 (0%)1 (7.7%)
 Trisomy 86 (11.3%)2 (13.3%)2 (13.3%)0 (0%)0 (0%)2 (15.4%)
 17p loss1 (1.9%)0 (0%)1 (6.7%)0 (0%)0 (0%)0 (0%)
 −20 or del(20q)2 (3.8%)0 (0%)1 (6.7%)0 (0%)0 (0%)1 (7.7%)
 Y loss1 (1.9%)1 (6.7%)0 (0%)0 (0%)0 (0%)0 (0%)
 Complex karyotype5 (9.4%)3 (20.0%)0 (0%)0 (0%)0 (0%)2 (15.4%)
NGS study
 Number of mutated gene3 (0–7)3 (0–5)3 (1–7)3 (1–6)2 (1–3)3 (0–7)
 ASXL1 & TET2 co-mutation12 (22.6%)3 (20.0%)5 (33.3%)2 (33.3%)0 (0%)2 (15.4%)
Splenomegaly9 (17.0%)3 (20.0%)3 (20.0%)2 (33.3%)0 (0%)1 (7.7%)
Transfusion dependency20 (37.7%)7 (46.7%)5 (33.3%)1 (16.7%)1 (25.0%)6 (46.2%)
Treatment regimen
 HMA8 (15.1%)2 (13.3%)4 (26.7%)1 (16.7%)0 (0%)1 (7.7%)
 HSCT5 (9.4%)0 (0%)1 (6.7%)3 (50.0%)0 (0%)1 (7.7%)
3-year outcome
 Progression8 (15.1%)1 (6.7%)5 (33.3%)1 (16.7%)0 (0%)1 (7.7%)
 Death14 (26.4%)4 (26.7%)5 (33.3%)1 (16.7%)0 (0%)4 (30.8%)
Abbreviations: MDS/MPN, myelodysplastic/myeloproliferative neoplasm; CMML, chronic myelomonocytic leukemia; MDS/MPN-N, MDS/MPN with neutrophilia; MDS/MPN-SF3B1-T, MDS/MPN with SF3B1 mutation and thrombocytosis; MDS/MPN-NOS, MDS/MPN not otherwise specified; WBC, white blood cell; Hb, hemoglobin; PLT, platelet; NGS, next-generation sequencing; HMA, hypomethylating agents; HSCT, hematopoietic stem cell transplantation; PFS, progression-free survival; OS, overall survival.
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MDPI and ACS Style

Park, M.-S.; Choi, D.-H.; Jang, J.H.; Jung, C.W.; Kim, H.-J.; Kim, H.-Y. Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1. J. Clin. Med. 2025, 14, 7074. https://doi.org/10.3390/jcm14197074

AMA Style

Park M-S, Choi D-H, Jang JH, Jung CW, Kim H-J, Kim H-Y. Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1. Journal of Clinical Medicine. 2025; 14(19):7074. https://doi.org/10.3390/jcm14197074

Chicago/Turabian Style

Park, Min-Seung, Dae-Ho Choi, Jun Ho Jang, Chul Won Jung, Hee-Jin Kim, and Hyun-Young Kim. 2025. "Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1" Journal of Clinical Medicine 14, no. 19: 7074. https://doi.org/10.3390/jcm14197074

APA Style

Park, M.-S., Choi, D.-H., Jang, J. H., Jung, C. W., Kim, H.-J., & Kim, H.-Y. (2025). Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1. Journal of Clinical Medicine, 14(19), 7074. https://doi.org/10.3390/jcm14197074

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