Chul Won Jung

To describe the post-transplant outcomes in patients with myelofibrosis stratified by the Dynamic International Prognostic Scoring System (DIPSS) risk at transplantation, and to identify clinical factors associated with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed the data of 42 patients with myelofibrosis who underwent allo-HSCT at Samsung Medical Center between 2014 and 2023. OS was estimated using the Kaplan–Meier method and compared using the log-rank test. Exploratory Cox proportional-hazard regression analyses were performed to assess independent associations with OS. At transplantation, 28 patients (66.7%) had Intermediate (Int-1/2) and 14 (33.3%) had High DIPSS risk. OS differed significantly by DIPSS risk group (log-rank P = 0.0034): the median OS was 15.2 months (95% confidence interval [CI], 7.2–NR months) in the Intermediate-risk group versus 6.4 months (95% CI, 3.3–35.1 months) in the High-risk group. All 14 patients in the High-risk group (100%) and 14 of 28 patients in the Intermediate-risk group (50%) died during follow-up. The 1-, 2-, and 3-year OS rates in the Intermediate- and High-risk groups were 57.1% vs. 28.6%, 50.0% vs. 14.3%, and 50.0% vs. 7.1%, respectively. In an exploratory multivariable analysis adjusted for hematopoietic cell transplantation-specific comorbidity index and donor type, DIPSS High-risk disease remained independently associated with inferior OS (adjusted hazard ratio [HR], 2.91; 95% CI, 1.27–6.63; P = 0.011). No other clinical variable, including age (≥ 60 vs. < 60 years; P = 0.16 by log-rank), achieved statistical significance. DIPSS High-risk disease at transplantation was associated with uniformly poor post-transplant survival in this single-center cohort. These hypothesis-generating findings underscore the importance of transplant timing before progression to high-risk disease, and warrant validation in larger multicenter studies. The online version contains supplementary material available at 10.1007/s44313-026-00142-5.

Background: DDX41 is one of the most frequent adult-onset myeloid neoplasm predisposition gene, yet its biology remains incompletely defined. This study investigated the frequency, spectrum, and clinical characteristics of DDX41 variants in Korean patients with hematologic malignancies, including the patterns of co-occurring somatic variants. Methods: We retrospectively reviewed 716 patients with hematologic malignancies who underwent targeted next-generation sequencing. In patients with germline DDX41 variants, clinicopathologic features, co-occurring variants, variant allele frequency (VAF) distributions, and survival were analyzed. Results:DDX41 variants were identified in 34/716 patients (4.7%), including 33 germline carriers (4.6%), occurring most frequently in AML (6.2%) and MDS (11.1%). Patients with germline DDX41 variants had a median age of 68 years, were predominantly male (69.7%), and commonly had normal karyotypes (72.7%), with similar features in AML and MDS except for lower platelet counts in AML (p = 0.025). The most common germline DDX41 variants were Y259C (20.6%), A500fs (14.7%), E7* (11.8%), V152G (11.8%), and D139G (8.8%), with null variants predominating in AML and missense variants in MDS (p = 0.002). Somatic DDX41 variants occurred in 63.6% of patients with germline DDX41 variants, with R525H being the most frequent (48%), while non-DDX41 somatic variants were detected in 78.8% of patients, most commonly involving ASXL1, DNMT3A, SRSF2, and TET2, which appeared at lower VAFs, suggesting late acquisition. Conclusions: This study demonstrates ethnic-specific DDX41 variant patterns in Korean myeloid neoplasm patients, with biallelic alterations potentially involved in early leukemogenesis. These findings provide further insight into the unique features of DDX41-associated myeloid neoplasms.

Hyun-Young Kim, M.D., Ph.D., Boram Kim, M.D., Min-Seung Park, M.D., Ph.D., Jong-Ho Park, Ph.D., Hee Young Ju, M.D., Ph.D., Keon Hee Yoo, M.D., Ph.D., Jun Ho Jang, M.D., Ph.D., Chul Won Jung, M.D., Ph.D., and Hee-Jin Kim, M.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0300

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.

Objectives: Despite its utility, interpreting multiparameter flow cytometry (MFC) data for hematologic malignancy remains time-intensive and complex. This study evaluated the applicability of two dimensionality reduction (DR) algorithms, t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), to MFC data of hematologic malignancy. Methods: A total of 237 samples were re-analyzed by t-SNE- and UMAP-based gating: 80 with acute leukemia orientation tube panel, 42 with B-cell lymphoma (BCL) panel, 45 with multiple myeloma (MM) panel, 40 and 30 with measurable residual disease (MRD) panels for B-cell acute lymphoblastic leukemia (B-MRD) and MM (MM-MRD), respectively. Each result was compared to the manual gating, and sensitivity and precision were assessed using BCL and B-MRD panels. Results: Compared to manual gating, DR-based gating demonstrated agreements over 95.0 % for all MFC panels, and quantitative correlations ( ρ ) exceeded 0.94. Both t-SNE- and UMAP-based gating showed a sensitivity and negative predictive value of 100 %. Also, in one sample each from the BCL and MM-MRD panels, DR-based gating identified populations that were missed by manual gating. Sensitivity evaluation showed that both t-SNE- and UMAP-based gating successfully identified MRD populations down to the lowest MRD level of 10 ^−5.30 when applying primary-gating strategy for CD19-positive population. Precision evaluation showed coefficient of variation below 10 % across all levels. Conclusions: This study shows that DR-based gating streamlines data interpretation and minimizes overlooked populations, demonstrating significant potential as a valuable tool in MFC analysis for hematologic malignancies.

Background: Germline GATA2‐deficiency usually manifests as immunodeficiencies and myeloid neoplasms and sometimes with dermatological diseases, including warts, panniculitis, and skin cancers.Case: We report a 36‐year‐old woman with germline GATA2‐deficiency who developed Merkel cell carcinoma followed by acute myeloid leukemia. Molecular analysis revealed a germline GATA2 S447R variant, not reported from the previous reported case, suggesting a potential association with Merkel cell carcinoma.Conclusion: This case broadens the spectrum of solid cancers linked to GATA2‐deficiency, emphasizing the need for considering primary immunodeficiency in young patients with myeloid neoplasms or rare skin cancers, facilitating early detection and treatments.

Min-Seung Park, M.D., Boram Kim, M.D., Jun Ho Jang, M.D., Ph.D., Chul Won Jung, M.D., Ph.D., Hee-Jin Kim, M.D., Ph.D., and Hyun-Young Kim, M.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2024.0190

The ETV6::ABL1 fusion defines a subgroup of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions. We report a case of extramedullary involvement and leukemic transformation in myeloproliferative neoplasm (MPN), where ETV6::ABL1 was initially overlooked but later detected in the blast phase. ETV6::ABL1 burden was very low during the MPN phase but increased substantially during the blast phase. This correlation between ETV6::ABL1 burden and disease phenotype indicated that an immature leukemic clone is the sole carrier of ETV6::ABL1, suggesting that ETV6::ABL1 is not the primary driver of the MPN phase. Moreover, only the blast phase revealed somatic mutations in RUNX1 and STAG2, or complex karyotype, while the MPN phase revealed no molecular and cytogenetic abnormalities. Therefore, it remains uncertain whether the small clone of ETV6::ABL1 influenced the manifestation of MPN or if another underlying driver was responsible for the MPN phase, necessitating further research.

Lee JH, et al. Korean J Adult Nurs. 2024 Aug;36(3):191-202. https://doi.org/10.7475/kjan.2024.36.3.191