Analysis of factors influencing the prognosis of pediatric acute myeloid leukemia based on minimal residual disease with different detection methods

Pediatric LSC3 (pLSC3) Score Derived from DNMT3B-CD34-GPR56 As a Prognostic Tool to Predict AML Patient Outcome: Results from Two Independent Pediatric AML Cohorts

EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia.

Integrating Genomics and Functional Phenotypes to Refine Risk Assessment in Acute Myeloid Leukemia across the Age Spectrum: Insights from Singapore

Mutation Profiling Reveals Novel Epigenetics and Splicing Mutations in Chemorefractory Pediatric AML

Combining Melphalan or Thiotepa with an Intensive Conditioning Regimen Significantly Reduces Relapse Rates in Minimal Residual Disease-Positive (MRD+) Pediatric Acute Myeloid Leukemia Patients Post Haploidentical Hematopoietic Stem Cell Transplantation

A DNA Methylation Signature Predicts Clinical Outcome in Pediatric AML Patients

Impact of Allogeneic Hematopoietic Stem Cell Transplantation in First Complete Remission and Additional Cytogenetic Aberrations at Diagnosis on Prognosis in 1256 Pediatric Patients with KMT2A-Rearranged Acute Myeloid Leukemia: A Retrospective Study By the I-BFM-SG

Impact of SAMHD1 Pharmacogenetics on Clinical Outcome in Pediatric AML

The purpose of this study was to evaluate the correlation of long non-coding RNA maternally expressed gene 3 (Lnc-MEG3) with disease features, treatment response, and survival in pediatric acute myeloid leukemia (AML) patients.Among 92 de novo pediatric AML patients (before treatment and after 1 course of induction) and 40 controls, bone marrow mononuclear cells were obtained. Then, Lnc-MEG3 expression was determined by reverse transcription quantitative polymerase chain reaction. After 1 course of standard induction therapy of pediatric AML patients, complete remission (CR) was assessed. Furthermore, event-free survival (EFS) and overall survival (OS) were determined according to follow-up data.Lnc-MEG3 was reduced in pediatric AML patients compared with controls. In pediatric AML patients, Lnc-MEG3 was correlated with French-American-Britain subtypes and lower Chinese Medical Association risk stratification, while it was not associated with cytogenetic features, FLT3-ITD mutation, CEBPA mutation, NPM1 mutation, WT1 mutation, or National Comprehensive Cancer Network risk stratification. After 1 course of treatment, Lnc-MEG3 exhibited an up-regulation trend. Furthermore, Lnc-MEG3 was of no difference before treatment between patients with and without CR, while elevated Lnc-MEG3 and change of Lnc-MEG3 after 1 course of treatment were associated with increased CR rate. Additionally, increased Lnc-MEG3 expression before treatment was associated with longer EFS but not OS, while enhanced Lnc-MEG3 expression after 1 course of treatment was correlated with both prolonged EFS and OS.Lnc-MEG3 may have clinical significance as a biomarker for assisting with disease management, treatment optimization, and prognosis improvement in pediatric AML patients.

Recurrent Gene Mutations in Pediatric Patients with AML By Targeted Sequencing ―the Jccg Study, JPLSG AML-05―

Minimal Residual Disease after the 2nd Induction Course Predicted Outcomes in Chinese Children with Acute Myeloid Leukaemia Treated According to the C-Huanan-AML 15 Protocol

DNA repair system is critical in maintaining genome stability and integrity in response to various exogenous and endogenous stress factors. It is a multistep processes involving several enzymes including XRCC1 (X-ray repair cross-complementing group1) protein which plays a vital role in DNA repair activities and therefore is important for maintenance of genetic stability. The current study involves investigation of single nucleotide polymorphisms (SNPs) in the XRCC1 gene and their association with clinical response in pediatric acute myeloid leukemia (AML) patients treated with cytarabine (ara-C) based anti-leukemic chemotherapy in the St. Jude AML02 clinical trial. The St. Jude AML02 trial enrolled 232 AML patients less than 22 years of age, randomized to receive induction I therapy containing high-dose cytarabine or low-dose cytarabine plus daunorubicin and etoposide. A total of eighteen XRCC1 SNPs were genotyped using MALDI-TOF based Sequenom assay and screened for association with 3 endpoints, namely: in vitro ara-C LC50 determined in leukemic cells obtained at diagnosis (which was measured by treating leukemic cells in vitro with varying concentrations of ara-C), event free survival (EFS) and overall survival (OS). Jung statistic was used to determine association of the number of minor alleles with EFS and OS. Association of genotypes with EFS and OS was measured using Cox regression models while considering previously identified prognostically important variables. Our results showed significant association of 4 XRCC1 SNPs with survival and ara-C LC50 in pediatric AML patients. Three of these were present in the coding region, while one was a regulatory SNP located in the promoter region of the XRCC1 gene. XRCC1 SNPs have also been shown to be associated with cancer susceptibility and survival in previous studies. Our results now demonstrate clinical significance of XRCC1 SNPs in pediatric AML and suggest a role of these SNPs as prognostic factors in AML chemotherapy. These results might open up opportunities for tailored chemotherapy based on genomic markers to improve therapeutic outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-228. doi:1538-7445.AM2012-LB-228

BCOR and BCORL1 mutations in pediatric acute myeloid leukemia

Acute myeloid leukemia (AML) is a common leukemia with low cure rate and poor prognosis among pediatric patients. The regulation of AML immune microenvironment and methylation remains to be explored. Pediatric and adult AML patients differ significantly in epigenetic factors, and the efficiency of treatment modalities varies between the two groups of patients. We collected mRNA, miRNA and DNA methylation data from pediatric AML patients across multiple databases. Differentially expression genes were identified, and a gene-miRNA regulatory network was constructed. Prognostic risk models were established by integrating LASSO and Cox regression, and a nomogram was generated. Based on this model, we investigated tumor-infiltrating immune cells and cell communication, analyzing the biological functions and pathways associated with prognostic factors. Furthermore, the relationships between all prognostic factors and gene modules were explored, and the impact of these factors on treatment modalities was determined. We developed an efficient prognostic risk model and identified HOXA9, SORT1, SH3BP5, mir-224 and mir-335 as biomarkers. We validated these findings in an external dataset and observed a correlation between age and risk in pediatric patients. AML samples with lower risk scores have a better prognosis and higher expression of immune-upregulated biomarkers, and have lower immune scores. Furthermore, we detected discrepancies in immune cell infiltration and interactions between high- and low-risk group samples, which affected the efficacy of immunotherapy. We evaluated all prognostic factors and predicted the effect of immunotherapy and medicine. This study comprehensively investigated the role of methylation signature genes in pediatric AML at the level of genomes and transcriptomes. The research aims to enhance the risk stratification, prognosis evaluation and assessment of treatment effectiveness of AML patients. This study also highlight the uniqueness of pediatric AML and foster the development of new immunotherapy and targeted therapy strategies.

Objective To explore the clinical characteristics and prognosis of core binding factor(CBF)positive acute myeloid leukemia(AML)in children. Methods Eighty-five children with AML who were not acute promyelocytic leukemia (APL) and Downs syndrome were enrolled in this study and received more than one course of chemotherapy from Jun.2007 to Jun. 2012 in Children's Hospital of Soochow University.They were divided into low-risk group, medium-risk group, high-risk group according to national unity stratification criteria to confirm their survival condition, analyze the effection of prognosis of sex, FAB type, initial white blood cell number, CBF, chromosome, complete remission course, central nervous system leukemia(CNSL), relapse, hematopoietic stem cell transplantation(HSCT). Forty cases with CBF positive AML were evaluated with Kaplan-Meier survival curves of 5-year overall survival(OS) rate and event-free survival(EFS) rate, CBF negative AML as control group. Results Five-year OS rates of low-risk, intermediate-risk and high-risk group were (66.5±11.6)%, (54.5±14.4)% and(42.7±7.2)% respectively, there was significant difference(χ2=6.085, P=0.048); and the 5-year EFS rates were (62.2±14.0)%, (54.5±14.4)% and(41.9±7.3)% respectively, there was no significant difference(χ2=1.060, P=2.589). Cases of distribution of CBF positive AML were 22/23 cases in low-risk group, 3/11 cases in medium-risk group and 15/51 cases in high-risk group.Twenty-three cases survived in CBF positive AML group, 24 cases survived in control group, and their 5-year OS rates were(51.8 ± 8.8)%, (50.6±7.6)%, respectively.Ten cases relapsed, including 6 cases with CBF positive(3 cases death) and 4 control cases(2 cases death). Twenty cases received HSCT, including 5 cases with CBF positive (1 case death) and 15 control cases(3 cases death). COX regression multivariate analysis showed that gender, numbers of course of induction chemotherapy to remission and HSCT were individually statistic significance for pediatric AML's prognosis while the FAB classification, initial leukocyte count and central nervous system leukemia had no effect on prognosis. Conclusions There is no significantly statistic difference between CBF positive AML and its control in chemotherapy group.The survival rate in control group and all cases in pediatric AML could be obviously improved by HSCT. Key words: Core binding factor; Leukemia; Myeloid; Acute; Prognosis; Child