Cancer Research and Treatment

Cytokine-Primed MSCs Enhance Antitumor Immunity-Associated Gene Expression Without Promoting AML Cell Growth: Na Hee Lee, Byungchan Kim, Keon Hee Yoo; Received June 2, 2025 Accepted September 10, 2025 Published online September 11, 2025; DOI: https://doi.org/10.4143/crt.2025.583 [Accepted]

Abstract PDF: Purpose
Mesenchymal stromal cells (MSCs), while regarded as promising immunomodulatory tools, have raised concerns in recent studies for their potential to promote tumor growth or facilitate immune evasion. These risks are particularly relevant in hematologic malignancies, where MSCs have been used to mitigate graft-versus-host disease or support hematopoietic engraftment. This study aimed to evaluate the effects of cytokine-primed MSCs on acute myeloid leukemia (AML) cells, with a focus on both safety and immunomodulatory efficacy.
Materials and Methods
Wharton’s jelly-derived MSCs were primed with interferon-gamma (IFN-γ), interleukin-6, lipopolysaccharide, and tumor necrosis factor-alpha, followed by co-cultured with AML cell lines. AML cell viability was measured by CCK-8 assay. RNA sequencing and qPCR were performed to assess gene expression profiles under each priming condition.
Results
Cytokine priming MSC did not result in significant changes in AML cell viability (p > 0.05), supporting the safety of this approach. Meanwhile, IFN-γ priming significantly upregulated genes involved in immune modulation and apoptosis, including IDO1, TNFSF10, ICAM1, and chemokines CXCL9, CXCL10, and CXCL11.
Conclusion
Cytokine priming, particularly with IFN-γ, enhanced the immunomodulatory gene expression of MSCs without promoting AML cell proliferation. Although direct cytotoxic effects were not observed in co-culture experiments, the absence of increased leukemic cell growth under any priming condition supports the biological safety of this approach. These findings provide a strong foundation for further in vivo studies to assess the therapeutic applicability of primed MSCs in hematologic malignancies while ensuring oncologic safety.

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RMRP-Induced Chemo-Resistance in Relapsed and Refractory Acute Myeloid Leukemia via Mitochondrial Dysfunction: Yijing Zhao, Hanfei Guo, Yalan Zhou, Li-Ting Niu, Na Wu; Received March 11, 2025 Accepted August 6, 2025 Published online August 7, 2025; DOI: https://doi.org/10.4143/crt.2025.281 [Accepted]

Abstract PDF: Purpose
Relapsed and refractory acute myeloid leukemia (R/R AML) has a poor prognosis due to chemotherapy resistance. Mitochondrial dysfunction contributes to this resistance, but the role of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in R/R AML remains unclear.
Materials and Methods
Mass spectrometry identified molecules linked to chemoresistance in AML. The role of RMRP was examined by assessing its impact on mitochondrial transfer in the AML bone marrow microenvironment. Transmission electron microscopy and western blotting were used to study mitochondrial function and autophagy in RMRP-knockdown AML cells.
Results
RMRP was overexpressed in R/R AML, and its silencing sensitized AML cells to chemotherapy drugs. RMRP knockdown reduced mitochondrial respiratory capacity, mtDNA copy numbers, and mitochondrial gene transcription. It also led to altered mitophagy markers and decreased mitochondrial methylation. Immunoprecipitation revealed RMRP-TERT complex formation, suggesting a role in post-transcriptional regulation of mitochondrial function and ROS production.
Conclusion
High RMRP expression in R/R AML is linked to mitochondrial dysfunction and chemotherapy resistance, providing new insights into potential therapeutic strategies to overcome drug resistance in this disease.

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Uncovering Putative Causal Non-Coding RNAs in Acute and Chronic Myeloid Leukemia: A Genome-Wide Mendelian Randomization Study: Sunwoo Jung, Ji-Won Kim, Buhm Han; Received April 3, 2025 Accepted June 24, 2025 Published online June 25, 2025; DOI: https://doi.org/10.4143/crt.2025.377 [Accepted]

Abstract PDF: Purpose
Although non-coding RNAs (ncRNAs) have often been implicated in various cancers, their causal roles in acute (AML) and chronic myeloid leukemia (CML) remain unclear. Here, we conducted a genome-wide two-sample Mendelian randomization (MR) study to investigate the causal effects of a comprehensive set of ncRNAs on AML and CML.
Materials and Methods
We used summary statistics of blood expression quantitative trait loci (eQTL) from the eQTLGen consortium (31,684 European participants) as exposure data. Genome-wide association study summary statistics from the FinnGen study (AML: 322 cases; CML: 303 cases) and UK Biobank (UKBB) (AML: 318 cases; CML: 153 cases) served as outcome data. The generalized inverse-variance weighted (GIVW) method was used as the primary MR method. Two additional MR methods (generalized MR-Egger and weighted median), sensitivity analyses, and the HEIDI test were further employed to support our findings.
Results
Upregulated HCG22 and RP11-42I10.1 were causally linked to increased AML risk, while the GMDS-AS1 locus was positively associated with increased CML risk. We highlight these ncRNAs for their consistent significance across all three MR methods, with no evidence of bias in sensitivity analyses (F-test, Cochran’s Q-test, MR-Egger intercept, MR-PRESSO global test) and no indication of confounding from the HEIDI test. Primarily discovered in FinnGen (FDR_GIVW<0.05), their significance was validated in UKBB (P_GIVW<0.05). Upon validation with an independent linkage disequilibrium reference panel, they remained robust.
Conclusion
This study provides evidence of causal relationships between ncRNAs and two ML subtypes, notably highlighting HCG22 and RP11-42I10.1 in AML and the GMDS-AS1 locus in CML.

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Hematologic malignancy

Literature-Guided 6-Gene Signature for the Stratification of High-Risk Acute Myeloid Leukemia: Jong Keon Song, Dong Hyeok Lee, Hyery Kim, Sang-Hyun Hwang; Cancer Res Treat. 2025;57(4):1207-1217. Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1114

Abstract PDF Supplementary Material PubReader ePub: Purpose
Acute myeloid leukemia (AML) shows significant heterogeneity in therapeutic responses. We aimed to develop a gene signature for the stratification of high-risk pediatric AML using publicly available AML datasets, with a focus on literature-based prognostic gene sets.
Materials and Methods
We identified 300 genes from 12 well-validated studies on AML-related gene signatures. Clinical and gene expression data were obtained from three datasets: TCGA-LAML, TARGET-AML, and BeatAML. Least absolute shrinkage and selection operator–Cox regression analysis was used to perform the initial gene selection and to construct a prognostic model using the The Cancer Genome Atlas (TCGA) database (n=132). The final gene signature was validated with two independent cohorts: BeatAML (n=411) and TARGET-AML (n=187).
Results
We identified a six-gene signature (ETFB, ARL6IP5, PTP4A3, CSK, HS3ST3B1, PLA2G4A), referred to as the literature-based signature 6 (LBS6), that was significantly associated with lower overall survival rates across the TCGA (high-risk [HR], 4.2; 95% confidence interval [CI], 2.59 to 6.81; p < 0.001), BeatAML (HR, 1.52; 95% CI, 1.17 to 1.96; p=0.001), and TARGET (HR, 2.05; 95% CI, 1.36 to 3.08; p < 0.001) datasets. The high-LBS6 score group exhibited significantly poorer five-year event-free survival compared to the low-LBS6 score group (HR, 2.09; 95% CI, 1.38 to 3.15; p < 0.001). After adjusting for key risk factors, including gene mutations (WT1, FLT3, and NPM1), protocol-based risk group, white blood cell count, and age, the LBS6 score was independently associated with worse survival rates in validation cohorts.
Conclusion
Our literature-driven approach identified a robust gene signature that stratifies AML patients into distinct risk groups. The LBS6 score shows promise in redefining initial risk stratification and identifying high-risk AML patients.

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Pediatric cancer

Outcome of Intensive Therapy for Children with Relapsed Acute Myeloid Leukemia: A Single Institution Korean Study: Jae Wook Lee, Jae Won Yoo, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2022;54(4):1230-1239. Published online December 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1011

Abstract PDF Supplementary Material PubReader ePub

Purpose
Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution.
Materials and Methods
The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR).
Results
Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free.
Conclusion
Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.

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TREML2 enhances sensitivity of acute myeloid leukemia cells to chemotherapy by inhibiting the NF-κB/CXCL10 pathway
Xin Zhang, Shuheng Yan, Xuehong Zhang, Dan Huang, Jiayin Zhou, Xiaoting Song, Yuchao Hao, Xijia Wang, Jinsong Yan
Blood Science.2025; 7(2): e00223. CrossRef
Diagnosis and Treatment of Pediatric Acute Megakaryoblastic Leukemia with NUP98::KDM5A Rearrangement: Case Report
Hyemin Kang, Suejung Jo, Jae Won Yoo, Seongkoo Kim, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Chae Yeon Lee, Myungshin Kim
Clinical Pediatric Hematology-Oncology.2024; 31(2): 56. CrossRef

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Epidemiology of Acute Leukemia among Children with Down Syndrome in Korea: Young Bae Choi, Keon Hee Yoo; Cancer Res Treat. 2022;54(2):572-578. Published online August 10, 2021; DOI: https://doi.org/10.4143/crt.2021.368

Abstract PDF PubReader ePub

Purpose
Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS.
Materials and Methods
Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016.
Results
Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group.
Conclusion
Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

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Does Down syndrome affect the prognosis of acute lymphoblastic leukemia? A systematic review and meta-analysis
Francisco Cezar Aquino de Moraes, Artur de Oliveira Macena Lôbo, Vitor Kendi Tsuchiya Sano, Caroline R. M. Pereira, Lucyana Barbosa Cardoso Leão, Thiago Xavier Carneiro, Rommel Mario Rodríguez Burbano
Expert Review of Hematology.2025; 18(11): 961. CrossRef
Prevalência de neoplasias malignas em pessoas com síndrome de Down: uma revisão de escopo
Válery Muniz de Sousa, Mônica Vilela Heimer, Danilo Bastos Moreno, Sandra Conceição Maria Vieira
Caderno Pedagógico.2025; 22(13): e21693. CrossRef
Cancer risks related to intellectual disabilities: A systematic review
Amina Banda, Jenneken Naaldenberg, Aura Timen, Agnies van Eeghen, Geraline Leusink, Maarten Cuypers
Cancer Medicine.2024;[Epub] CrossRef

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Optimization and Limitation of Calcium Ionophore to Generate DCs from Acute Myeloid Leukemic Cells: Thanh-Nhan Nguyen Pham, Bo-Hwa Choi, Hyun-Kyu Kang, Chun-Chi Jin, Nguyen Hoang Tuyet Minh, Sang-Ki Kim, Jong-Hee Nam, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Ik-Joo Chung, Je-Jung Lee; Cancer Res Treat. 2007;39(4):175-180. Published online December 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.4.175

Abstract PDF PubReader ePub

Purpose

Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI.

Materials and Methods

To generate leukemic DCs, leukemic cells (4×10⁶ cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days.

Results

Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2×10⁶ cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells.

Conclusion

Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells.

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The plasticity and potential of leukemia cell lines to differentiate into dendritic cells
QINGWEI GUO, LELING ZHANG, FU LI, GUOSHENG JIANG
Oncology Letters.2012; 4(4): 595. CrossRef

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