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YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is an inflammatory glycoprotein secreted by different types of cells, such as inflammatory cells. The levels of this protein are elevated in the serum or plasma of patients with different types of cancer, and high concentrations are associated with poor prognosis and short survival in patients with liver, breast, lung, bladder and endometrial cancers. In Mexico, acute lymphoblastic leukemia (ALL) is the most common type of cancer affecting the pediatric population. The prognosis of patients with ALL is difficult to establish. Hence, the objective of the present study was to analyze the plasma levels of YKL-40 in Mexican children with ALL and investigate its role as a prognostic factor. A case-control study was performed in a population of 90 children aged 1-18 years, among whom 45 had ALL and 45 were hematologically healthy. The levels of YKL-40 in plasma samples were measured using ELISA and were found to be significantly higher in children with ALL compared with those in controls (P<0.0001). Children with ALL who had high plasma levels of YKL-40 (≥36.34 ng/ml) had shorter survival compared with those with low levels (<36.34 ng/ml; P<0.05). The findings of the present study revealed that the YKL-40 plasma level, age/initial leukocyte count and central nervous system invasion were associated with the prognosis of children with ALL [odds ratio (OR)=6.06, 95% confidence interval (CI): 1.1-31.6, P=0.03; OR=8.53, 95% CI: 1.2-58.2, P=0.03; and OR=6.45, 95% CI: 1.01-41.2, P=0.04, respectively]. Therefore, YKL-40 plasma levels may serve as a prognostic biomarker in pediatric patients with ALL., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Rivas-Alarcón et al.)

The present study analyzed the mRNA expression levels of genes involved in the transport and metabolism of methotrexate (MTX) (RFC1, ABCC1, ABCB1, GGH, FPGS, ATIC, TS, MTHFR, MTRR, MS and MTHFD1) in patients with acute leukemia (AL). The expression levels of the examined genes were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with AL (ALL:50/AML:19) and 66 healthy individuals. The mRNA expression levels of RFC1, MS, MTRR, MTHFR and ABCB1 were decreased (P<0.05), while those of GGH, FPGS, TS and MTHFD1 (P<0.05) were overexpressed in patients with AL. Patients with high mRNA levels of GGH (OR=4.28, 95% CI=1.29-14.14), TS (OR=7.14, 95% CI 1.84-27.81), MTHFR (OR=4.81, 95% CI=1.31-17.64), ABCB1 (OR=4.61, 95% CI=1.33-15.97) and ABCC1 (OR=5.50, 95% CI=1.12-27.06) had a higher chance of relapse. Interestingly, high mRNA levels of RFC1 are a protective factor in the risk of AL relapse (OR=0.22, 95% 0.06-0.80). The results of the present study indicated that deregulation of folate pathway gene expression is associated with poor prognosis in AL and that the expression levels of these markers could serve as novel molecular targets for the treatment of patients with AL.

Background: Polymorphisms in folate-related genes are closely related to the development of cancer. The 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms are associated with an increased risk of susceptibility to pediatric ALL., Objective: The aim of this study was to illustrate the association between 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms and ALL in a Mexican population., Materials and Methods: This study was conducted in 60 pediatric ALL patients and 60 healthy individuals. The 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms were detected by the PCR-RFLP method., Results: Our investigation revealed that the 5,10-MTHFR 677 C/T and 5,10-MTHFR 677T/T genotypes are associated with susceptibility to pediatric ALL (OR = 1.9, 95% IC = 1.36-12.09, p = 0.012 and OR = 2.8, 95% CI = 1.49-22.82, p = 0.011, respectively). Likewise, the G/A genotype from the RFC1 80G>A polymorphism showed an increased ALL risk compared to RFC1 G80G genotype (OR = 3. 3, 95% CI = 1.75-8.87, p = 0.002)., Conclusion: Therefore, our results suggest that the 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms are factors involved in the susceptibility to ALL in Mexican population., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Dihydrofolate reductase (DHFR) has an important function in DNA synthesis and is a target of methotrexate, which is a crucial treatment option for acute lymphoblastic leukemia (ALL). However, the number of studies conducted to date on DHFR expression in childhood ALL is limited. The aim of the present study was to determine whether the expression of DHFR is associated with survival in childhood ALL. The expression of DHFR in 96 children with ALL and 100 control individuals was determined using reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the expression of DHFR mRNA in children with ALL was significantly increased (P<0.001), compared with that in the control group. In addition, increased levels of DHFR mRNA were observed in patients with B-cell lineage, compared with patients with T-cell lineage ALL (P<0.05). The Kaplan-Meier estimator analysis revealed that children with ALL who exhibited increased levels of DHFR mRNA had a decreased overall survival time (P<0.05). It was observed that certain patient prognostic features (including age, sex, white blood cell count and high DHFR expression), are associated with poor survival (log-rank test, P<0.05). Therefore, the results of the present study indicated that DHFR upregulation is a factor for poor survival in ALL.

MicroRNAs (miRNAs) play an essential role in the development and progression of acute leukemia (AL). miR-24 promotes the survival of hematopoietic cells. However, little is known concerning the function of miR-24 in human AL. The aim of the present study was to investigate the clinical significance of miR-24 expression in AL. miR-24 expression in 147 patients with AL and 100 healthy individuals was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). The results showed that compared with the healthy individuals, the expression of miR-24 in AL patients was significantly higher (p<0.001). In addition, miR-24 was expressed at significantly higher levels in acute myeloid leukemia (AML) patients and at significantly lower levels in acute lymphoblastic leukemia (ALL) (p<0.001). More importantly, Kaplan-Meier analysis showed that AL patients with high miR-24 expression tended to have shorter overall survival (p<0.05). In the multivariate analysis stratified for known prognostic variables, miR-24 was identified as an independent prognostic marker. Our data indicated that miR-24 upregulation was associated with poor prognosis in AL. miR-24 was identified for the first time as an independent marker for predicting the clinical outcome of AL patients.

Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. Polymorphisms in the gene coding for DHFR have been associated with adverse event treatment. This study evaluated the effect of the -A317G and C829T polymorphisms in the DHFR gene on survival and risk of relapse of ALL. Seventy patients with ALL and 100 healthy individuals were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. An association between the polymorphisms and the risk of relapse was found (p<0.05); patients with the -317G/G genotype were found to have an 8.55 (95% CI 1.84-39.70) higher chance of relapse and carriers of the 829T/T genotype had a 14.0 (95% CI 1.13-172.63) higher chance of relapse. Other variables, such as age and leukocyte count, were associated (p<0.05) with the risk of relapse of the disease. Individuals with the G/G and T/T genotype of the -A317G and C829T polymorphisms had poorer survival compared to other genotype groups (log-rank test; p<0.05). Although preliminary, these data seem to suggest a role for the DHFR polymorphisms in the risk of relapse of ALL and the mortality risk in these patients.

This study evaluated the association of -401C/T and +452C/T polymorphisms of gamma-glutamyl hydrolase and the risk of relapse to acute lymphoblastic leukemia. Genotyping was performed in 70 children with acute lymphoblastic leukemia and 140 healthy children. An association between the -401C/T polymorphism and the risk of relapse was found (p=0.028), patients with the -401T/T genotype have 10.83 (95% CI 1.30-90.14) more chance of a relapse of leukemia. No association was found between the +452C/T polymorphism and the risk of relapse. Therefore, our investigation suggests that the -401C/T polymorphism in the gamma-glutamyl hydrolase may be a factor involved in the generation of relapse to disease in patients with ALL., (Copyright 2009 Elsevier Ltd. All rights reserved.)