Lihua Yang’s research while affiliated with Southern Adventist University and other places

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Publications (47)


Leukemia burden impacts the efficacy and toxicity of blinatumomab in pediatric B-cell acute lymphoblastic leukemia
  • Preprint

May 2025

Weiling Yan

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Shaoyan Hu

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Wenjin Gao

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[...]

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Xiao-Jun Xu

Schematic depiction of the synthesis and mechanism of Met-CuS@DSH. A Schematic depiction of the Met-CuS@DSH synthesis process. B Underlying mechanism of radiosensitization of Met-CuS@DSH
Preparation and characterization of Met-CuS@DSH. A Schematic representation of the synthetic strategy employed for Y and L monomers. B Characterization of ssDNA and Y and L DNA monomers via polyacrylamide gel electrophoresis. C Photographs of the solution-state Y and L DNA monomers and the gel-state DSH (nucleic acid material within withe circles). D Schematic diagram illustrating the synthesis of DSH. E SEM image of DSH (scale bars: 100 μm). F Rheology analysis of DSH. G Schematic representation of the synthesis of Met-CuS@DSH. H Fluorescence microscopy images of Met-CuS@DSH by the confocal microscope. I In vitro CT images of CuS@DSH and Met-CuS@DSH with different concentrations. J In vitro infrared images of PBS, CuS@DSH and Met-CuS@DSH with a 980 nm laser irradiation for 10 min (0.51 W/cm²)
Bidirectional regulation of ROS for ROS strategy in vitro.A Fluorescence images of NPC cells with JC-1 aggregates (red) and monomers (green) in different groups. Scale bars: 10 μm. B Relative ATP content of NPC cells in different groups. C Activity of mitochondrial respiratory chain complex I in different groups. D Scheme depicting the in vitro NPC cells culture O2 concentration testing. E Cell O2 levels of NPC cells in different treatments. F Western blot analysis of HIF-1α expression after treatments. G Fluorescence micrographs depict the cellular response of NPC cells exposed to hypoxia probes following various treatment groups (scale bars: 200 μm). H GSH levels analysis results of NPC cells in different groups. I–J Quantification of intracellular ROS levels following various in vitro treatment groups. I–IV represent PBS, Met@DSH (Met concentration of 20 mM), CuS@DSH (CuS concentration of 288 µM), Met-CuS@DSH groups (Met and CuS concentrations of 20 mM and 288 µM). NS means no significance; **P < 0.01; ***P < 0.001; ****P < 0.0001
In vitro anti-tumor effect of Met-CuS@DSH A Flow cytometry analysis which is used to analyze the biosafety of different groups. B Quantitative analysis of the biosafety flow cytometry analysis. C Cell viability of the NPC cells 24 h after treatments. D Flow cytometry analysis of necrosis and apoptosis of cells following various treatments. E Quantitative analysis of the apoptosis flow cytometry analysis. F Fluorescence micrographs of the NPC cells underwent co-staining with Live Dye (green) and Nuclei Dye (red) (scale bars: 200 μm). I–VI represent PBS, Laser + Ray, Met-CuS@DSH, Met-CuS@DSH + Laser, Met-CuS@DSH +Ray, Met-CuS@DSH + Laser + Ray groups. NS means no significance; ****P < 0.0001
Bidirectional regulation of ROS for radiosensitization strategy in vivo. A Micro-PET images with ¹⁸F-FMISO after being treatments of saline, Met@DSH, CuS@DSH and Met-CuS@DSH (withe circles highlighted the cross-sectional view of Micro-PET). B Photoacoustic images of mice. C Fluorescence micrographs analysis results of tissue sections incubated with HIF-1α following different treatments (scale bars: 100 μm). D Infrared images of tumor sites in vivo under laser irradiation (980 nm, 0.51 W/cm², 10 min) after the treatments of PBS/saline, CuS@DSH and Met-CuS@DSH, respectively. E The CT scanning images of the tumor sites in vivo showed the enrichment of CuS in tumors (withe circles highlighted the tumor sites, I-IV represent different layers)

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Bidirectional regulation of reactive oxygen species for radiosensitization in nasopharyngeal carcinoma
  • Article
  • Full-text available

February 2025

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4 Reads

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1 Citation

Radiotherapy (RT) is the primary treatment modality for nasopharyngeal carcinoma (NPC). However, the tumor microenvironment (TME)-induced radioresistance often compromises its therapeutic efficacy. Herein, we propose an innovative bidirectional radiosensitization strategy for NPC. Specifically, we have encapsulated metformin (Met) and copper sulfide nanoparticles (CuS NPs) within injectable DNA supramolecular hydrogels (DSH) to create a novel radiosensitizer, Met-CuS@DSH. This radiosensitizer not only effectively reverses tumor hypoxia to promote reactive oxygen species (ROS) generation but also significantly inhibits glutathione (GSH)-mediated ROS scavenging, thereby achieving bidirectional radiosensitization by enhancing ROS production and suppressing its scavenging. This strategy significantly improves the therapeutic effect of NPC while reducing the RT dose (3 Gy in total), which provides a promising approach for overcoming the radioresistance of NPC caused by TME. Graphical Abstract

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NOTCH1 gene Fusions Occur Frequently in Refractory or Relapsed (R/R) T-Cell Lymphomablastic Lymphoma

November 2024

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3 Reads

Blood

Background : T-cell lymphoblastic lymphoma (T-LBL) developed from immature precursor T cells, occurs mostly in children and adolescents. It is generally confined to a tissue lesion and may progress rapidly or relapse if not properly treated. Previous T-LBL genetic studies have shown high frequency of NOTCH1/FBXW7 and PI3K-AKT signaling gene mutations somewhat similar to T-ALL. Additionally, recent reports with limited cases suggested NOTCH1 gene fusion (NOTCH1r) was another kind of exclusive oncogenic driver event of T-LBL accompanied with higher relapse rate. However, large scale verification, further discovery of mechanisms, novel molecular features, and prognostic biomarkers are still urgently needed. Method: Retrospective analyses were performed for target sequencing of 203 T-LBL cases tested in our lab between April 2019 and July 2024. Among those, 90 patients were refractory or relapsed (R/R) including those relapsed after HSCT, and they were admitted to Beijing GoBroad Boren hospital for further therapy. NOTCH1 gene fusions and hotspot gene mutations were analyzed and annotated with an in-house workflow. Clinical and molecular features of these R/R T-LBL cases were then further characterized and analyzed. We also performed survival analyses for the NOTCH1r patients to consolidate the recent clinical findings. Results: NOTCH1 r were frequently observed with a much higher incidence of 25.6% (23/90) in our R/R as compared to 10.6% (12/113) in other patients without detailed clinical information (p < 0.01). The median age of the 9 female (39.1%) and 14 male (60.9%) NOTCH1r R/R T-LBL patients was 15.0 (IQR: 9.0-31.0) years, while the median age of the 12 female (17.9%) and 55 male (82.1%) non-NOTCH1r R/R cases was 12.5 (IQR: 9.3-14.0) years. Female seem to have a higher NOTCH1r incidence than male (p < 0.01), while the disease onset age between NOTCH1r and non-NOTCH1r group was not significantly different (p = 0.08). The bone marrow involvement was rare in NOTCH1r R/R cases (1/11, 9.21%) than that of non-NOTCH1r (28/42, 66.7%, p < 0.01), similar to previous report. A total of five NOTCH1 fusion partner genes, i.e., IKZF2 (9/23, 39.1%), TRB (5/23, 21.7%), TSPOAP1-AS1(4/23, 17.4%), IKZF1(3/23, 13.0%), and TRA (2/23, 8.7%) were discovered. All the fusions of NOTCH1 with these genes were previously reported as driver event in sporadic cases. The hotspot IKZF2/1 genes fused to NOTCH1 with a breakpoint in either exon 27 or 28 (NM_017617.5), result in a chimeric transcription factor protein retaining the IKZF2/1's DNA-binding domain and the NOTCH1's transmembrane and intracellular subunit. The other three genes fused to NOTCH1 with wide-range breakpoints located between intron 24 and exon 34, which may play a divergent pathogenic mechanism. Only 1 NOTCH1r patient (4.3%) harbored a NOTCH1/FBXW7 gene mutation, while 32 of 67 (47.8%) non-NOTCH1r patients harbored NOTCH1/FBXW7 gene mutation, indicating the mutual exclusivity of the two types (p < 0.01). Additionally, 9 of 23 NOTCH1r patients (39.1%) carried PI3K-AKT pathway gene mutations, which was much higher than 7.5% of non-NOTCH1r patients (5/67, p < 0.01). Median follow-up time for all the 23 R/R NOTCH1r patient was 24.5 (95% CI:15.9-24.7) months. The one year overall survival (OS) rate was 94.7% (95% CI: 85.2-100%), and the mOS was 30.4 (95% CI: 30.4-NA) months. The one year cumulative incidence of relapse rate (CIR) was 29.9% (95% CI: 11.0-49.4%), which tends to be much higher than the overall five year CIR of 12.2% as show in the EURO-LB02 trial study, further consolidating the recent findings of NOTCH1r's T-LBL. Conclusion: NOTCH1 gene fusion with divergent partner genes occurred frequently in R/R T-LBL. These oncogenic driver events were mutually exclusive with NOTCH1/FBXW7 gene mutations. However, these fusions accompanied frequently with PI3K-AKT pathway alteration, which were also regarded as worse prognostic factors. The one year CIR of 29.9% was much higher than the reported overall five year CIR of 12.2%.


The Mutational Profile and Fusion Landscape of Chinese Pediatric B-Cell Lymphoblastic Lymphoma Patients

November 2024

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4 Reads

Blood

#Yang li and Ling Jin contribute equally to this article. *Corresponding to both Qinlong Zheng (zhengql@gobroadhealthcare.com) and Yonghong Zhang (zhangyongh@gobroadhealthcare.com). Background: B-cell lymphoblastic lymphoma (B-LBL) is a hematologic malignancy that originates from immature precursor B-cells and is less common in pediatric lymphoblastic lymphoma than T-cell lymphoblastic lymphoma. Currently, patients are stratified based on disease stage, as biological risk-factors have not yet been identified. A comprehensive understanding of B-LBL molecular status may help to improve the clinical management of these patients. Aims: The purpose of this study was to analyze the genetic features of Chinese pediatric B-LBL patients and to examine their associations with patient outcomes and clinical indicators. Methods: A total of 280 Chinese children with B-LBL treated at multiple clinical centers of the China Network for Childhood Lymphomas (CNCL) from 2017 to 2023 were included in this retrospective study. The patients were treated with a CNCL-NHL-2017-LBL treatment protocol. Targeted next-generation sequencing (t-NGS) with a panel spanning 262 lymphoma-associated genes was performed on tumor samples from 51 T-LBL patients. The associations of molecular variation with survival rates as well as with relapse and other clinical factors were analyzed. Results: This study enrolled a cohort of 280 pediatric patients diagnosed with B-LBL, with a median age of 5.8 years (range: 1-16 years) and a male-to-female ratio of 1.3:1. The median follow-up duration for our cohort was 43.7 months (95% CI: 38.2-49.1 months). We analyzed the mutational landscapes, and a total of 53 driver genes with somatic mutations were identified in 51 B-LBLs. The most frequently mutated genes were NRAS (12%), followed by FLT3 (10%), IKZF1(10%), KRAS (10%), ASXL2 (8%), CREBBP (6%) and KMT2D (6%). The recurrent mutated genes in pediatric B-LBL were mainly involved in RAS signaling pathway. Survival analysis revealed that patients with KMT2D mutations had shorter OS than patients without these mutations (log-rank p=0.008). In subsequent analysis, we collected fusion genes from 70 patients, of which the higher percentage fusion genes were TEL::AML1 (n=16, 23%), E2A::PBX1 (n=16, 23%), MLL rearranged (MLL-r, n=16, 23%), TCF3::PBX1 (n=5, 7%) and P2RY8::CRLF2 (n=5, 7%). Survival outcomes for patients with different fusion genes were analyzed, with the EFS of MLL-r positive patients being significantly worse than that of MLL-r negative patients (log-rank p<0.001). Further analysis of the distribution of gene mutations in patients with different clinical characteristics revealed that mutations in RAS pathway-related genes, including NRAS and KRAS, were detected only in patients with clinical stage IV. A high frequency of IKZF1 mutations was observed in patients with craniofacial, central nervous system (CNS), and bone marrow invasion. Additionally, the presence of P2RY8::CRLF2 in craniofacial invasion (13% vs. 3%) and E2A::PBX1 in CNS invasion (35% vs. 19%) was greater in patients with these clinical features than in those without these features. These findings suggest a correlation between genetic alterations and the severity of clinical symptoms, warranting further investigation. Conclusion: This study presents the first comprehensive molecular characterization of B-LBL in Chinese pediatric patients. There is a high incidence of mutations in genes involved in RAS signaling pathway in pediatric B-LBL. LYST mutations and MLL rearranged might be associated with poor outcomes in children with B-LBL.These results increase our understanding of the genetic heterogeneity of B-LBL in children and may pave the way for molecular risk adapted treatment protocols for B-LBL patients.


Adverse events of all patients
Leukemia burden impacts the efficacy and toxicity of blinatumomab in pediatric B-cell acute lymphoblastic leukemia

October 2024

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6 Reads

Background Blinatumomab has demonstrated its efficacy and safety in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). The objective of this analysis was to describe the responses and toxicities of blinatumomab in pediatric patients with different leukemic burdens in the bone marrow. Methods We enrolled patients aged 0-18 years who were diagnosed with CD19-positive B-ALL and treated with blinatumomab between January 2021 and May 2023 from 14 centers in China. Results A total of 307 patients were enrolled in this analysis. The complete remission (CR) rate was 72.1% among 61 patients with ≥5% blasts(non-complete remission, NCR group), of whom 90.9% achieved minimal residual disease (MRD) negativity. Among 93 patients with <5% blasts but multiparametric flow cytometry MRD (MFC-MRD) positive(MRD+ group), 96.8% achieved MRD negativity. Of the 153 MFC-MRD negative patients(MRD- group), 60.0% and 65.5% turned quantitative polymerase chain reaction MRD (qPCR-MRD) or next-generation sequencing MRD (NGS-MRD) negative, respectively. Additionally, Patients in the MRD+ and MRD- groups had significantly better outcomes than those in the NCR group, with 30-month OS rates of 91.6% (95% CI: 0.857-0.979), 95.3% (95% CI: 0.915-0.993), and 77.6% (95% CI: 0.674-0.894), respectively (P<0.001), and 30-month RFS rates of 90.7% (95% CI: 0.847-0.972), 93.3% (95% CI: 0.890-0.979), and 64.4% (95% CI: 0.495-0.837), respectively (P<0.001). There was no statistically significant difference in OS between the patients who achieved MFC-MRD negativity in the NCR group and those in the MRD+ group, with 30-month OS rates of 85.7% (95% CI: 0.745-0.987) and 93.2% (95% CI: 0.881-0.986), respectively (P=0.270). In this study, 41% of patients experienced grade ≥3 adverse events (AEs), with hematological toxicity being the most common (32.9%). The severe adverse events, such as cytokine release syndrome (CRS) and neurotoxicity, occurred at a low rate, particularly grade ≥3, at 3.6% and 2.6%, respectively. Conclusion Overall, these results indicate that blinatumomab is effective and well-tolerated. Patients with a lower leukemia burden before blinatumomab administration tend to have better overall survival and relapse-free survival with fewer AEs.


Visualizing cancer resistance via nano-quenching and recovery detector of CD44

July 2024

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12 Reads

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9 Citations

Drug resistance to chemotherapy in cancers remains significant clinical challenges. CD44 modulates cellular adhesion, migration and growth, which plays a pivotal role in driving cancer resistance and even recurrence. Despite ongoing efforts, accurate, safe, and real-time dynamic monitoring techniques for CD44 expression remain inadequate in guiding the management of drug-resistant cancer treatment. In this study, we developed a nano-quenching and recovery detector of CD44 (Cy3-AptCD44@BPNSs) for visualizing cancer drug resistance. The fluorescence recovery of the detector is directly related to the CD44 expression level on cancer cells, which can be used to indicate the degree of drug resistance. It’s confirmed that downregulating CD44 expression on cancer cells results in a corresponding decrease in the fluorescence intensity of the detector, which enables precise and dynamic monitoring of CD44. In addition, the Cy3-AptCD44@BPNSs also exhibited specificity in detecting CD44. This visualizing strategy may open up a wide range of possibilities for rapid recognition to cancer drug resistance, which is more efficient and flexible. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-024-02732-w.


Patient enrollment and disposition.
Bone pain scores FLACC, face, legs, activity, cry, and consolability; WBFPRS, Wong-Baker’s facial pain rating.
Median absolute neutrophil count after PEG-rhG-CSF ANC, absolute neutrophil count.
One-way sensitivity and probabilistic sensitivity analysis (A) Tornado diagram for one-way sensitivity analyses (B) Cost-effectiveness plane for PEG-rhG-CSF compared to rhG-CSF. The x-axis represented the difference in incremental cost-effectiveness and the Y-axis the difference in costs between PEG-rhG-CSF and rhG-CSF; (C) Cost-effectiveness acceptability curve.
Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study

July 2024

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15 Reads

Background High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3–4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3–4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.


The α- and β-diversity of gut microbiota in children with ALL during the induction chemotherapy. The α-diversity indices measure the total amount of different species (richness) and/or how balanced the relative abundance of species are (evenness) in a microbial ecosystem (within a single sample). Comparison of the (A) Chao1 index (indicates richness), (B) Observed species (indicates richness), (C) Simpson index (indicates evenness), and (D) Shannon index (indicates both richness and evenness). The β-diversity calculates the degree of similarity and distance based on phylogenetic trees and measures the difference between the composition of two microbial communities. (E) The Bray-Curtis dissimilarity matrix and PERMANOVA were performed to measure the gradual shifts in the overall compositions of the gut microbiota. (F) The Bray-Curtis distance was calculated to investigate the extent of microbial changes. Each point represents a sample. Data are represented as mean ± SD, *p < 0.05, **p < 0.01, ***p < 0.001
The gut microbial profile shifted remarkably during induction chemotherapy. (A-B) Relative abundances of gut microbiota at the phylum level in children with ALL during induction chemotherapy, clustered in groups (A) or individually (B). (C-D) Relative abundances of gut microbiota at the species level in children with ALL during induction chemotherapy, clustered in groups (C) or individually (D). (E) The microbiota that are significantly different in relative abundance and biological significance based on LEfSe analysis. (F) The relative abundances of microbiota that are significantly different between different timepoints. Data are represented as mean ± SD
The shifts in microbial functional pathways during induction chemotherapy. (A-B) Relative abundances of microbial functional pathways at the three timepoints during induction chemotherapy, clustered in groups (A) or individually (B). (C) The microbial functional pathways that are significantly different between the three timepoints based on LEfSe analysis. (D) The relative abundances of microbial functional pathways that are significantly different between the three timepoints. Data are represented as mean ± SD
Receiver operating characteristic (ROC) model. The ROC based on Bifidobacterium longum at T0 predict infectious complications during chemotherapy with the area under the curve (AUC) of 0.720 (95% CI: 0.5632–0.8768, p = 0.0187)
Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection

June 2024

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27 Reads

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2 Citations

Annals of Clinical Microbiology and Antimicrobials

Background Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown. Methods Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy. Results The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720. Conclusions Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy. Trial registration The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).


Survival curves of pediatric cell acute lymphoblastic leukemia (BCP‐ALL) in IKZF1 deletions (IKZF1del) group and IKZF1 wild‐type (IKZF1wt) group. (A) The cumulative disease‐free survival (DFS) of IKZF1del group and IKZF1wt group. (B) The cumulative overall survival (OS) of IKZF1del group and IKZF1wt group. (C) The cumulative relapse rates (CIR) of IKZF1del group and IKZF1wt group. (D) The treatment‐related mortality (TRM) of IKZF1del group and IKZF1wt group.
Subgroup analysis of the associations between IKZF1 status and outcome. (A) Hazard ratios for DFS in pediatric patients in the IKZF1del and IKZF1wt groups according to the risk factors. (B) Hazard ratios for OS in pediatric patients in the IKZF1del and IKZF1wt groups.
Survival curves of pediatric BCP‐ALL with IKZF1del treated with non‐intensive and intensive chemotherapy. (A) The DFS of the pediatric BCP‐ALL with IKZF1del treated with non‐intensive and intensive chemotherapy. (B) The OS of the pediatric BCP‐ALL with IKZF1del treated with non‐intensive and intensive chemotherapy. (C) The DFS of the pediatric BCP‐ALL with Ph+/IKZF1del treated with non‐intensive and intensive chemotherapy. (D) The OS of the pediatric BCP‐ALL with Ph+/IKZF1del treated with non‐intensive and intensive chemotherapy. (E) The DFS of the pediatric BCP‐ALL with Ph‐/IKZF1del treated with non‐intensive and intensive chemotherapy. (F) The OS of the pediatric BCP‐ALL with Ph‐/IKZF1del treated with non‐intensive and intensive chemotherapy.
Prognosis of pediatric BCP‐ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG‐2016 study

Background IKZF1 deletion (IKZF1del) is associated with poor prognosis in B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP‐ALL prognosis has not been determined. Methods A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP‐ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. Results The BCP‐ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3‐year DFS: 88.7% [95% CI: 83.4%–94.0%] vs. 93.5% [95% CI: 92.0%–94.9%], P = .021; 3‐year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3‐year TRM (6.4% [95% CI: 2.3%–10.5%] vs. 2.9% [95% CI: 1.9%–3.8%], P = .025). However, the 3‐year CIR was comparable between the two groups (5.7% [95% CI: 1.8%–9.5%] vs. 3.7% [95% CI: 2.6%–4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3‐year DFS was remarkably improved from 53.6% ± 20.1% with non‐intensive chemotherapy to 100% with intensive chemotherapy (P = .026). Conclusions Pediatric BCP‐ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.


Citations (21)


... Understanding its underlying molecular mechanisms and immune microenvironment is crucial for developing effective therapeutic strategies. Recent advances in molecular and cellular analysis techniques have provided unprecedented opportunities to explore the intricate relationships between various components within the tumor microenvironment [1][2][3][4]. ...

Reference:

Mendelian randomization analysis reveals potential association between allergic rhinitis and nasopharyngeal carcinoma
Bidirectional regulation of reactive oxygen species for radiosensitization in nasopharyngeal carcinoma

... In comparison, aptamers in the free state can bind analytes more efficiently with advantages such as small size, low steric hindrance, and good dispersibility. Recently, a nano-quenching and recovery detector for the CD44 antigen was developed by utilizing multi-layer black phosphorus nanosheets (BPNSs) and a dispersed Cy3-labelled CD44 aptamer [22]. The aptamers can attach to BPNSs via the van der Waals force and detach from BPNSs due to the target recognition reaction. ...

Visualizing cancer resistance via nano-quenching and recovery detector of CD44

... Another research delved deeper into the metabolic pathways of the gut microbiota in children with ALL undergoing chemotherapy, identifying significant alterations in pathways such as pyruvate fermentation to acetate and lactate, and the assimilatory sulfate reduction pathway. These metabolic changes, along with shifts in microbial diversity and composition, were linked to the prediction of infectious complications, with Bifidobacterium longum at baseline predicting infections during the first month of chemotherapy [51]. ...

Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection

Annals of Clinical Microbiology and Antimicrobials

... The combination of these drugs and chemotherapy achieved sustained clinical and molecular-level T A B L E 2 Risk factors for event-free survival (EFS) and overall survival (OS) according to univariate and multivariate Cox regression models. relief in children with LCH, and the side effects were tolerable, 19 which is a promising therapeutic option for adult LCH in the future. Limitations of the present study include its single-centre design, which restricts the generalizability of our findings. ...

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study

Journal of Cancer Research and Clinical Oncology

... Some studies also indicate that MFC-MRD evaluation post-second chemotherapy cycle correlates with survival rates in KMT2A-r AML. 30 Achieving MRD negativity earlier may indicate better chemotherapy sensitivity and predict favourable outcomes. However, the optimal time point is yet to be determined. ...

Prognostic significance of multiparametric flow cytometry minimal residual disease at two time points after induction in pediatric acute myeloid leukemia

BMC Cancer

... Fusarium solani (Fig. 9, upper section): This type of Fusarium produces oval-shaped conidia, with numerous small conidia showing septation (division). Some large conidia exhibit a "matte" shape with rounded ends, often divided into three segments 43 . ...

Disseminated Fusarium solani infection in a child with acute lymphocytic leukemia: A case report and literature review
  • Citing Article
  • December 2023

Medicine in Microecology

... The amplifier increased free radical production and conserved oxygen within the tumor to maximize the radiotherapeutic effect, demonstrating an innovative solution to the tumor microenvironment's hypoxiainduced limitations on radiotherapy effectiveness (87). Together, these studies underscore the remarkable potential of aptamer-based multi-agent systems in enhancing radiosensitization through precise targeting, improved therapeutic synergy, and overcoming tumorspecific barriers in radiotherapy applications (87). ...

Enhancing the sensitization of neuroblastoma to radiotherapy by the construction of a dual-channel parallel free radicals nanoamplifier

Materials Today Bio

... ROR1 is a receptor expressed during embryonic development, in some adult healthy tissues such as the gastrointestinal tract, and in human epithelial cancers [77]. Meng et al. [53] analyzed RNA expression data from public databases and found high expression of ROR1 in CRC, cholangiocarcinoma, clear cell renal carcinoma, and prostate cancer. ROR1 expression was also con-firmed by flow cytometry in CRC cell lines. ...

The onco-embryonic antigen ROR1 is a target of chimeric antigen T cells for colorectal cancer
  • Citing Article
  • June 2023

International Immunopharmacology

... Despite these results, studies suggest that it is still not fully proven whether clinical deterioration in pediatric oncohematological patients is preceded by changes in vital signs that can be rapidly identifiedIn study E14, the Pediatric Sequential Organ Failure Assessment (pSOFA) score demonstrated the highest predictive validity for hospital mortality, followed by PEWS and the Pediatric Critical Illness Score (PCIS). The study concluded that using various scoring systems can aid in early sepsis identification, monitoring clinical status, recognizing critical illness, and determining the optimal timing for PICU transfer, ultimately improving patient outcomes(26).However, PEWS stood out for being simpler and more practical in clinical practice.This fact is supported by results from another study that also demonstrated the efficacy of PEWS as an indicator for monitoring changes in the clinical condition of children in the hematology oncology unit, serving as a basis for adjusting the level of care and ICU transfers (44).Finally, in studies E12 and E15, the authors sought to develop their own prognostic scoring system to identify patients in clinical deterioration with a high mortality rate, improving the accuracy of predictions. The authors justified their studies by noting that, currently, there is no reliable and validated scoring system that determines the admission of onco-hematological patients to the ICU or predicts their long-term survival, which complicates early detection and interventions(27) (24). ...

Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit
  • Citing Article
  • June 2023

Pediatric Blood & Cancer

... 15 For CBF-AML patients with ASXL1 mutation especially those with higher WBC, research has shown that it is linked to poorer outcomes, including reduced OS and RFS, emphasizing the prognostic significance, consistent with findings across myeloid malignancies, where ASXL1 mutations are considered a poor prognostic factor. 93,[97][98][99][100] Moreover, the prognosis of pediatric AML with the ASXL1 mutation in a substantial Chinese multicenter cohort in the southern region of China was enhanced by HSCT (hematopoietic stem cell transplantation), aligning with findings in studies involving adult patients. 97,101 The impact of mutations on epigenetic regulation like the ASXL family and its interaction with other genetic abnormalities underscore the need for further research to understand its role in disease progression and therapy response in pediatric CBF-AML. ...

Clinical characteristics and prognosis analysis of patients with de novo ASXL1-mutated AML treated with the C-HUNAN-AML-15 protocol: A multicenter study by the South China Pediatric AML Collaborative Group