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

Acute myeloid leukemia (AML) is a malignant clonal hematologic disease from hematopoietic stem and progenitor cells. The isocitrate dehychogenase 2 (IDH2) gene mutation has been recently found, which may be associated with the course of AML. The incidence of IDH2 gene mutation in the patients with acute myeloid leukemia is high, especially in the AML patients with normal karyotype. Different subtypes of IDH2 mutation, or companing other molecular biology, will make different influence on clinical features and progress of patients with AML. IDH2 mutation is stable, which can be used as the test sign of AML and minimal residual disease (MRD), and for guiding the clinical treatment and predicting the progress. In this article, the research progress of IDH2 mutation in acute myeloid leukemia is reviewed.
Humans ; Isocitrate Dehydrogenase ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Neoplasm, Residual ; Prognosis

MRD detection in children leukemia has a potential importance to predict clinical outcome and to modify treatment protocols of the diseases. Although some patients with leukemia have achieved complete remission according to the clinical and morphological criteria, there are still very low numbers of malignant cells that can not be discriminated by morphology and remained in bone marrow, which is called minimal residual disease (MRD) and is the main reason leading to relapse. MRD detection has an important significance for designing treatment protocols. Several methods of MRD detection have been developed. These include conventional cytogenetics, fluorescence in situ hybridization (FISH), flow-cytometric immunophenotyping (FCM), Southern blot and polymerase chain reaction (PCR) techniques, etc. Each of these techniques has its advantages and disadvantages, so not all of them are suitable for clinical MRD detection because of several inherent disadvantages, such as limited sensitivity, time-consuming, high cost, or requiring high-quality DNA or RNA. For example, the sensitivities of conventional cytogenetics, FISH, FCM and Southern blot approaches for MRD monitoring are 10(-1) - 10(-2), 10(-2), 10(-3) - 10(-4) and 10(-1), respectively. Relatively, PCR can reach a good sensitivity of 10(-4) - 10(-6), and show more advantages, such as fast, specific, simple and low-cost, as well as minimal amounts of DNA or RNA for detection, etc., so PCR has its specific features for MRD detection. In this review, the progress on the detection technique for screening leukemia specific marker by muitiplex PCR and FQ-PCR in recent years are summarized.
Child ; Humans ; Leukemia ; diagnosis ; genetics ; Neoplasm, Residual ; diagnosis ; genetics ; Polymerase Chain Reaction ; methods ; Sensitivity and Specificity

OBJECTIVE: To observe the detection of fusion gene in children with acute lymphoblastic leukemia (ALL) of different immunophenotypes, and analyze the relationship between fusion gene and prognosis. METHODS: The clinical data of 86 children with ALL treated in the hospital from May 2015 to May 2020 were retrospectively analyzed, the immunophenotypes and the prognosis of children were recorded, the detection of fusion gene in ALL children with different immunophenotypes was compared, the relationship between detection of fusion gene and prognosis was analyzed. RESULTS: The results of bone marrow immunophenotype showed that there were 13 cases of T cell type and 73 cases of B cell type in 86 children with ALL. The detection rate of fusion gene SIL-TAL1 in ALL children with T cell type was significantly higher than that in ALL children with B cell type (P<0.05). The detection rates of fusion genes BCR-ABL1, E2A-PBX1 and TEL-AML1 in ALL children with B cell type were higher than those in ALL children with T cell type, but the differences were not statistically significant (P>0.05). Followed up for 8-12 months, recurrence was taken as the end point, the average follow-up time was (10.14±1.75) months, in 86 children with ALL 15 cases recurred (17.44%). The recurrence curve drawn by Kaplan-Meier method showed that the median recurrence time of 15 children with recurrent ALL was 9 months. The proportions of positive minimal residual disease and extramedullary infiltration in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (P<0.05). The detection rates of fusion genes BCR-ABL and SIL-TAL1 in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that positive minimal residual lesions, extramedullary infiltration, and detection of fusion genes BCR-ABL and SIL-TAL1 were risk factors for poor prognosis in children with ALL (OR>1, P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of combined detection of fusion gene BCR-ABL and SIL-TAL1 for predicting the poor prognosis of ALL children was >0.707, which had a certain predictive value. CONCLUSION There are differences in fusion genes among ALL children with different immunophenotypes, minimal residual disease, extramedullary infiltration, and fusion gene are associated with prognosis of ALL children. Fusion gene detection can be used as new method to predict the prognosis of children with ALL.
Child ; Humans ; Neoplasm, Residual ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Oncogene Proteins, Fusion/genetics*

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 study was purposed to investigate the significance of id4 gene promoter methylation in monitoring AML patients with complete remission (CR). Methylation specific-PCR (MS-PCR) were used to detect the status of promoter methylation of id4 gene in bone marrow samples from AML patients with CR who had accepted induction with DA or IA and 4 to 5 consolidation chemotherapy with Ara-C. The results showed that in the all 32 patients, 15 were found to show id4 promoter methylation and 7 out of the 15 were found relapsed or tendency to relapse in the following-up period. While all the 17 patients with id4 unmethylation were still in their CR status in the same period. In conclusion, id4 promoter methylation might be a predictor for relapse of AML patients with CR in certain degree.
DNA Methylation ; Humans ; Inhibitor of Differentiation Proteins ; genetics ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Neoplasm, Residual ; diagnosis ; genetics ; Promoter Regions, Genetic ; genetics

Child ; DNA Methylation ; Humans ; Leukemia ; classification ; drug therapy ; genetics ; Neoplasm, Residual ; Prognosis

In recent years, standardized treatment based on the risk stratification has been applied to clinical diagnosis and treatment of leukemia, which significantly improves the remission rate of ALL. However, relapse after remission remains an important challenge for long term efficacy. Chromosomal karyotype analysis is often used clinically to study the genetic features of ALL. As leukemia-specific markers, the cytogenetic and molecular genetic abnormalities can be used to evaluate prognosis and make an effective and optimal therapy. Furthermore, they are also used to track minimal residual disease. Therefore, the cytogenetic and molecular genetic abnormalities may become a monitor and a new target for the treatment of leukemia. This review briefly introduces the structure and physiological function of B-ALL associated cytogenetic and molecular genetic abnormalities, focusing on their prognostic effect on B-ALL.
Cytogenetic Analysis ; Humans ; Karyotyping ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Prognosis

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

The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification. Children with ETV6-RUNX1 or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.
Child ; Dasatinib ; Humans ; Neoplasm, Residual ; Philadelphia Chromosome ; Precision Medicine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*