OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To explore the correlation between single nucleotide polymorphisms (SNPs) of ARID5B gene and the risk of acute lymphoblastic leukemia (ALL) and minimal residual disease (MRD) in children of Hui and Han nationality in Ningxia. METHODS: In this case-control study, 54 ALL children and control group with matched age, sex and nationality were detected for the polymorphism of ARID5B gene using fluorescence resonance energy transfer technique, and the susceptibility of different ALL genotypes and their correlation with MRD were analyzed. RESULTS: There were no significant differences in genotype and allele frequency of rs10994982, rs7089424, rs10740055, rs7073837, rs4245595 and rs7090445 between the two groups (P >0.05). At the locus of rs10821936, the frequencies of T/T genotype and T allele in ALL group were significantly higher than those in the control group (both P < 0.05). The C/C genotype of ARID5B gene SNP rs10821936 was a risk factor for early MRD positive in ALL children ( P < 0.05). CONCLUSION ARID5B gene SNP rs10821936 is related to the development of childhood ALL and MRD.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Polymorphism, Single Nucleotide ; Case-Control Studies ; Neoplasm, Residual/genetics* ; DNA-Binding Proteins/genetics* ; Transcription Factors/genetics* ; Genotype ; Genetic Predisposition to Disease ; Gene Frequency ; Child ; Male ; Female ; Alleles ; Risk Factors ; Child, Preschool

Circulating tumor DNA (ctDNA) is emerging as a novel biomarker for tumor evaluation, offering advantages such as high sensitivity and specificity, minimal invasiveness, and absence of radiation. Currently, various techniques including gene sequencing and PCR are employed for ctDNA detection. The utilization of ctDNA for monitoring minimal residual disease (MRD) enables comprehensive assessment of tumor status and early identification of tumor recurrence, achieving a remarkable detection sensitivity of 0.01%. Therefore, ctDNA holds promise as a biomarker for early diagnosis, treatment response monitoring, and prognosis prediction in solid tumors. This article reviews the commonly used methods for detecting ctDNA and their advantages in evaluating tumor MRD and guiding clinical diagnosis and treatment.
Humans ; Circulating Tumor DNA/genetics* ; Neoplasm, Residual/genetics* ; Biomarkers, Tumor/genetics* ; Neoplasm Recurrence, Local ; Prognosis

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

With the advent of precision medicine, next-generation sequencing (NGS) is playing an increasingly important role in clinical oncology diagnosis and treatment with its advantages of high sensitivity, high accuracy, high efficiency and operability. NGS reveals the genetic characteristics of acute leukemia(AL) patients by screening for specific disease-causing genes to identify occult as well as complex genetic mutations in patients with AL, leading to early diagnosis and targeted drug therapy for AL patients, as well as to predict disease recurrence by detecting mnimal residual disease (MRD) and analyzing mutated genes to determine patient prognosis. NGS plays an increasingly important role in the diagnosis, treatment and prognosis assessment in AL, providing a direction for the pursuit of precision medicine. This paper reviews the research progress of NGS in AL.
Humans ; High-Throughput Nucleotide Sequencing ; Leukemia, Myeloid, Acute/genetics* ; Acute Disease ; Mutation ; Recurrence ; Neoplasm, Residual/genetics*

The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Neoplasm, Residual ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-ret/genetics*

Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ² test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×10⁹/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ²=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ²=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.
Male ; Female ; Humans ; Child ; Prognosis ; Philadelphia Chromosome ; Retrospective Studies ; Receptor, Platelet-Derived Growth Factor beta/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Neoplasm, Residual

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Child ; Female ; Male ; Humans ; High-Throughput Nucleotide Sequencing ; Neoplasm, Residual/genetics* ; Retrospective Studies ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Peritoneal metastasis of gastric cancer serving as the most frequent form of metastasis, is one of the leading causes of death. A portion of surgically treated patients often suffer from small peritoneal residual metastasis, which will lead to recurrence and metastasis of gastric cancer patients after surgery. Given these, the prevention and treatment of peritoneal metastasis of gastric cancer deserves more attention. Molecular residual disease (MRD) refers to the molecular abnormalities of tumor origin that cannot be found by traditional imaging or other laboratory methods after treatment, but can be found by liquid biopsy, representing the possibility of tumor persistence or clinical progress. In recent years, the detection of MRD based on ctDNA has gradually become a research hotspot in the prevention and treatment of peritoneal metastasis. Our team established a new method for MRD molecular diagnosis of gastric cancer, and reviewed the research achievements in this field.
Humans ; Stomach Neoplasms/pathology* ; Peritoneal Neoplasms/secondary* ; Liquid Biopsy ; Neoplasm, Residual/genetics*