Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.

UNASSIGNED: The purpose of this study is to investigate the genotype and allele distribution of MTHFR rs1801133 in the Chinese population, and to analyze the relationship between gene polymorphism of MTHFR rs1801133 and risk of childhood leukemia.
UNASSIGNED: Blood samples and clinical data of childhood leukemia cases (n=1132) and age-matched healthy controls (n=1053) were collected. Genotypes and allele distribution of MTHFR rs1801133 were detected by PCR-RFLP. Logistic regression model was generated to analyze the relation between MTHFR rs1801133 and susceptibility to childhood leukemia and the chemotherapy response.
UNASSIGNED: Age, sex, BMI and family history of tumor were comparable between childhood leukemia cases and healthy controls. Genotypes and allele distribution of MTHFR rs1801133 were remarkably correlated to the risk of childhood leukemia. Genotype risk of MTHFR rs1801133 was parallel to the susceptibility to childhood leukemia. Specifically, compared with people carrying AA allele of MTHFR rs1801133, higher risk of childhood leukemia may occur in people carrying AG+GG allele of MTHFR rs1801133 with a younger age (<15 years) or complete remission from chemotherapy.
UNASSIGNED: MTHFR rs1801133 gene polymorphism has a significant correlation with childhood leukemia. It is an important genetic susceptibility gene of childhood leukemia. The reliability of the results requires to be further validated by the high-quality research involving a large sample size in multi-center hospitals.
UNASSIGNED: Svrha ove studije je da se ispita distribucija genotipa i alela MTHFR rs1801133 u kineskoj populaciji i da se analizira odnos između polimorfizma gena MTHFR rs1801133 i rizika od leukemije u detinjstvu.
UNASSIGNED: Prikupljeni su uzorci krvi i klinički podaci slučajeva leukemije u detinjstvu (n = 1132) i zdravih kontrola odgovarajućeg uzrasta (n = 1053). Genotipovi i distribucija alela MTHFR rs1801133 detektovani su PCR-RFLP Model logističke regresije je generisan da analizira odnos između MTHFR rs1801133 i osetljivosti na leukemiju u detinjstvu i odgovora na hemoterapiju.
UNASSIGNED: Starost, pol, BMI i porodična istorija tumora bili su uporedivi između slučajeva leukemije u detinjstvu i zdravih kontrola. Genotipovi i distribucija alela MTHFR rs1801133 bili su u značajnoj korelaciji sa rizikom od leukemije u detinjstvu. Rizik od genotipa MTHFR rs1801133 bio je paralelan sa osetljivošću na leukemiju u detinjstvu. Konkretno, u poređenju sa ljudima koji nose AA alel MTHFR rs1801133, veći rizik od leukemije u detinjstvu može se javiti kod ljudi koji nose AG+GG alel MTHFR rs1801133 mlađe starosti (<15 godina) ili potpune remisije od hemoterapije.
UNASSIGNED: Polimorfizam gena MTHFR rs1801133 ima značajnu korelaciju sa dečjom leukemijom. To je važan gen genetske osetljivosti na dečju leukemiju. Pouzdanost rezultata treba da bude dodatno potvrđena visokokvalitetnim istraživanjem koje uključuje veliki uzorak u bolnicama sa više centara.

UNASSIGNED: This study was to comprehensively clarify the associations between single nucleotide polymorphisms (SNPs) in inflammatory genes and the susceptibility to childhood leukemia.
UNASSIGNED: Eligible articles were collected from the databases of PubMed, EMBASE, Cochrane Library, CNKI and Wan Fang. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimate the association strength by using the STATA 15.0 software.
UNASSIGNED: Sixteen studies were enrolled. These studies mainly evaluated SNPs in 13 genes, including C-X-C motif chemokine ligand 12 (CXCL12), toll-like receptor (TLR)-4, TLR6, TLR9, CD14, interleukin (IL)-1β, NLR family pyrin domain containing 3, IL-4, interleukin 4 receptor, IL-10, IL-13, macrophage migration inhibitory factor (MIF) and tumor necrosis factor-α. The meta-analysis indicated that CXCL12 rs1801157 (AG vs GG: OR = 1.99; 95%CI = 1.20-3.30; p = 0.008; AA + AG vs GG: OR = 1.92; 95%CI = 1.18-3.12; p = 0.009), TLR6 rs5743810 (TC vs TT: OR = 0.58; 95%CI = 0.39-0.85; p = 0.005), IL-10 rs1800871 (TC vs CC: OR = 1.19; 95%CI = 1.01-1.41; p = 0.044), rs1800872 (AC vs AA: OR = 1.53; 95%CI = 1.22-1.92; p < 0.001) and MIF rs755622 (CG versus GG: OR = 1.33; 95%CI = 1.07-1.67; p = 0.012) polymorphisms were associated with the risk of childhood leukemia. No significant correlations were found between SNPs in other genes and the childhood leukemia risk. Subgroup analyses of rs1800871 and rs1800872 confirmed the conclusions obtained in their overall meta-analytical processes.
UNASSIGNED: CXCL12 rs1801157, TLR6 rs5743810, IL-10 rs1800871, rs1800872 and MIF rs755622 polymorphisms may represent candidate biomarkers for the risk prediction of childhood leukemia.

Recent studies suggest that children born via cesarean section (CS) are predisposed to immune-mediated diseases later in life. The association between CS and childhood leukemia was investigated in this meta-analysis of observational studies. Two researchers independently searched PubMed, Web of Science, Embase, and Cochrane Library for literature on the association between CS and childhood leukemia before February 2022. And pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to determine the link between CS and childhood leukemia. The preliminary search resulted in 1321 articles and 16 articles were finally included after screening. The primary outcome was the risk of leukemia in children born via CS versus those born vaginally. The results revealed that having a CS was associated with an increased risk of childhood leukemia compared to having vaginal section (VS) (OR = 1.07, 95% CI: 1.02-1.13, p = 0.01), especially for acute lymphoblastic leukemia (ALL) (OR = 1.09, 95% CI: 1.03-1.16, p = 0.004). Children delivered via elective CS had a higher risk of ALL (OR = 1.18, 95% CI: 1.07-1.31, p = 0.001), but emergency CS did not. It is worth noting that neither emergency CS nor elective CS were found to be associated with acute myeloid leukemia. Compared to VS, CS increased the risk of leukemia in children, with elective CS significantly increasing ALL risk.

OBJECTIVE: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk.
METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed.
RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex.
CONCLUSIONS: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.

UNASSIGNED: Caveolae are plasma membrane subdomains of many mammalian cells that play critical roles in cellular processes, including endocytosis, signal transduction and tumorigenesis. Cavin proteins are essential for caveola formation, structure and function and are reported to be involved in various human diseases, but little is known about their expression and prognostic value in leukemia.
UNASSIGNED: We performed a detailed analysis of Cavin family mRNA expression levels in different cancer tissues vs. normal tissues via the ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) databases. Then, we used qRT-PCR and Western blotting to validate Cavin1-4 expression in 10 fresh leukemia samples. Moreover, we estimated their prognostic value in leukemia with the R programming language and GEPIA database.
UNASSIGNED: The expression of Cavin members is low in most human cancers, especially in leukemia. Cavin-1 and Cavin-2 are often more expressed in myeloid leukemia than lymphoblastic leukemia, but Cavin-4 has the opposite pattern. Interestingly, low expression of CAVIN1 and CAVIN4 is correlated with poorer outcome but low CAVIN2 expression is associated with a significantly better leukemia prognosis in leukemia.
UNASSIGNED: The Cavin family showed significant expression differences between leukemia and normal cells. High Cavin-2 and low Cavin-4 levels predict poor survival and could be promising subtype diagnosis and prognosis biomarkers for leukemia.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL.
METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL.
RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found.
CONCLUSIONS: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.

OBJECTIVE: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL).
METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653.
RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls.
CONCLUSIONS: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.