NK cells with decreased expression of multiple activating receptors is a dominant phenotype in pediatric patients with acute lymphoblastic leukemia.

NK cells have unique attributes to react towards cells undergoing malignant transformation or viral infection. This reactivity is regulated by activating or inhibitory germline encoded receptors. An impaired NK cell function may result from an aberrant expression of such receptors, a condition often seen in patients with hematological cancers. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide and NK cells have emerged as crucial targets for developing immunotherapies. However, there are important gaps concerning the phenotype and behavior of NK cells during emergence of ALL. In this study we analyze the phenotype and function of NK cells from peripheral blood in pediatric patients with ALL at diagnosis. Our results showed that NK cells exhibited an altered phenotype highlighted by a significant reduction in the overall expression and percent representation of activating receptors compared to age-matched controls. No significant differences were found for the expression of inhibitory receptors. Moreover, NK cells with a concurrent reduced expression in various activating receptors, was the dominant phenotype among patients. An alteration in the relative frequencies of NK cells expressing NKG2A and CD57 within the mature NK cell pool was also observed. In addition, NK cells from patients displayed a significant reduction in the ability to sustain antibody-dependent cellular cytotoxicity (ADCC). Finally, an aberrant expression of activating receptors is associated with the phenomenon of leukemia during childhood.

Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population. METHODS: A multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5'exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software. RESULTS: miR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05-2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23-23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04-298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found. CONCLUSION: Our findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.

Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children. Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis. Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21-1.93), rs1799929 (OR 1.96, 95% CI 1.55-2.49), and rs1208 (OR 1.44, 95% CI 1.14-1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30-1.71, OR 3.87, 95% CI 2.20-6.80, and OR 2.26, 95% CI 1.32-3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed. Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

[Sensitivity and specificity of the Tc-99m ciprofloxacin scan in pediatric osteomyelitis]. / Sensibilidad y especificidad del gammagrama ciprofloxacino-Tc99m en osteomielitis infantil.

INTRODUCTION: The Tc-99m-ciprofloxacin complex, introduced in 1993, has been extensively evaluated all over the world with good results for the diagnosis of active bacterial osteoarticular infections. There are only a few publications on the use of this procedure in pediatric ages. In our study we evaluated the efficacy of the Tc-99m ciprofloxacin scan for the diagnosis of osteoarticular infections in the pediatric population assessing its sensitivity, specificity, and positive and negative predictive value. MATERIAL AND METHODS: A retrospective, descriptive, observational study was done in 94 patients with clinical suspicion of osteoarticular infection in whom a Tc-99m ciprofloxacin bone scan was performed; the diagnosis was confirmed with intraoperative cultures and blood cultures. The results obtained with the Tc-99m ciprofloxacin scan and the culture reports were analyzed, as well as the sensitivity, specificity and the positive and negative predictive values of the Tc-99m ciprofloxacin scan. RESULTS: Among the patients with intraoperative and blood cultures, 80 cases (85.1%) were positive and 14 cases (14.9%) were negative for bone infection. In the Tc-99m ciprofloxacin scan 78 cases (83%) were found to be positive for infection and 16 cases (17%) were negative. There were two false negatives. We found a 97.6% sensitivity and 100% specificity, with a 100% positive predictive value and an 87.5% negative predictive value. CONCLUSION: The Tc-99m-ciprofloxacin complex is useful to make the differential diagnosis between inflammation and infection in pediatric patients in whom an osteoarticular infectious process is suspected.

[Minimally invasive surgery efficacy in children's forefoot]. / Eficacia de la cirugía mínimamente invasiva en el antepié de los ninos.

Minimally invasive surgery (MIS) in children's forefoot is a technique that permits minimum tissue trauma assisted by fluoroscopic control. We evaluated the results of this modality of surgery in problems such as: claw toes, hallux valgus, exostosis, hammer toe, and bunionectomy. We had a complication for using the procedure with more revolutions per minute (rpm), which remind us of the importance of using 2000-8000 rpm. We found that it is not commendable to make hypercorrections, due it increases they risk of recurrence. MIS is an excellent option in forefoot deformity correction in children leaving minimal scars and preserving the physis.