Describe the frequency of thrombotic and non-thrombotic clinical manifestations, laboratory, treatment and prognosis in patients with pediatric primary antiphospholipid syndrome.
A retrospective ...study was carried out in patients with a diagnosis of primary antiphospholipid antibody syndrome, under 16 years of age, under follow-up by the pediatric rheumatology service of the General Hospital, National Medical Center, La Raza, from January 2013 to December 2020. The antiphospholipid syndrome was defined when it met the laboratory criteria of the Sidney criteria and the presence of thrombosis or non-criteria manifestations of the disease (hematological, neurological, cutaneous, renal, cardiac or pulmonary). Demographic, clinical, laboratory, treatment, and prognosis data were collected.
We report 32 patients, 21 female (65%) and 11 male (35%), mean age 11.75 years, evolution time 16 weeks. Thrombosis 9 patients (28%), 1 arterial and 8 venous. Non-thrombotic manifestations; Hematologic: thrombocytopenia 22 patients (69%), autoimmune hemolytic anemia 13 (40%), Fisher-Evans syndrome 6 (19%), lupus anticoagulant with hypoprothrombinemia syndrome 2 (6%). Dermatological: livedo reticularis 20 (62%), skin ulcers 2 (6%), Raynaud's phenomenon 8 (25%). Neurological: epilepsy 1 (3%), migraine 3 (9%), chorea 1 (3%) and cognitive impairment 3 (9%). Renal in 4 (13%). Laboratory: prolonged aPTT 30 (93%), lupus anticoagulant 32 (100%), positive IgG anticardiolipin 20 (62%), positive IgM anticardiolipin 19 (60%). AntiB2GPI was performed in only 3 patients, being positive in all.
anticoagulation in patients with thrombosis, antiplatelet in 23 (72%), steroid 30 (94%), immunosuppressant 30 (94%) and rituximab 4 (12.5%). No deaths were reported.
The clinical characteristics of patients with pediatric primary antiphospholipid syndrome differ from those presented in adults, since non-thrombotic manifestations are more frequent in children, for which classification criteria that include these manifestations are necessary for a better characterization of the disease in pediatric population.
Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular ...features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson’s correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (
CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72,
and
NT5E
)
.
The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (
PLK1, CDC20, CDC45,
and
GADD45A
) and a low expression of
IL7R
and
PIK3CG,
which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for
PIK3CG
. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.
SARS-CoV-2 has spread throughout the world since 2019, changing in its genome and leading to the appearance of new variants. This gave it different evolutionary advantages, such as greater ...infectivity and/or a greater ability to avoid the immune response, which could lead to an increased severity of COVID-19 cases. There is no consistent information about the viral load that occurs in infection with the different SARS-CoV-2 variants, hence, in this study we quantify the viral load of more than 16,800 samples taken from the Mexican population with confirmed diagnosis of COVID-19 and we analyze the relation between different demographic and disease variables. We detected that the viral load caused by different variants differs only in the first two days after the onset of symptoms, being higher when infections are caused by the delta variant and lower when caused by omicron. Furthermore, the viral load appears to be higher in outpatients compared to hospitalized patients or in cases of death. On the other hand, no differences were found in the viral load produced in vaccinated and unvaccinated patients, nor did it differ between genders.
Background
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot ...be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether
LINC00173
is a biomarker in ALL and to explore its expression level in other human cancer types.
Methods
A nested case–control study including Mexican children with BCP-ALL was conducted.
LINC00173
expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively.
LINC00173
expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA).
Results
A lower expression of
LINC00173
in BCP-ALL cases compared to normal subjects was observed (
p
< 0.05). ALL patients who carry the
TCF3/PBX1
fusion gene displayed lower expression of
LINC00173
in contrast to other BCP-ALL molecular subtypes (
p
< 0.04).
LINC00173
underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213–3.120) and die (HR = 2.073, 95% CI = 1.211–3.547). Patients with
TCF3/PBX1
and underexpression of
LINC00173
had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04–29.71; OS: HR = 11.19, 95% CI = 26–32). TCGA data analysis revealed that underexpression of
LINC00173
is also associated with poor clinical outcomes in six new reported tumor types.
Conclusion
Our findings suggest that
LINC00173
is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of
LINC00173
and
TCF3/PBX1
and the risk to relapse and die in BCP-ALL, which is worse in
TCF3/PBX1-
positive cases displaying underexpression of
LINC00173.
Experimental studies are needed to provide insight into the
LINC00173
and
TCF3/PBX
relationship.
Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high ...prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.
Background and Aims Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an ...interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. Methods A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 ( PIP4K2A ), rs10821936 ( ARID5B ), rs7089424 ( ARID5B ) and rs2239633 ( CEBPE ) polymorphisms. Results Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5–2.4) and OR = 2.0, 95% CI (1.6–2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0–4.9) and OR 3.1, CI 95% (2.0–4.8), respectively). Otherwise, the rs7088318 ( PIP4K2A ) and rs2239633 ( CEBPE ) polymorphisms were not associated with ALL risk. Conclusions Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population.
Background and Aims It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase ( TPMT ) mutant allele carriers are at high risk to develop severe and potentially fatal ...hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. Methods We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5′exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). Results The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A . We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects ( p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. Conclusions TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment.
Tryptophan hydroxylase-type 2 (Tph2) is the first rate-limiting step in the biosynthesis of serotonin (5-HT) in the brain. The ophthalmic administration (Op-Ad) is a non-invasive method that allows ...delivering genetic vehicles through the eye and reaches the brain. Here, the murine
Tph2
gene was cloned in a non-viral vector (pIRES-hrGFP-1a), generating pIRES-hrGFP-1a-Tph2, plus the FLAG-tag. Recombinant Tph2-FLAG was detected and tested in vitro and in vivo
,
where 25 μg of pIRES-hrGFP-1a-Tph2-FLAG was Op-Ad to mice. The construct was capable of expressing and producing the recombinant Tph2-FLAG in vitro and in vivo
.
The in vivo assays showed that the construct efficiently crossed the Hemato-Ocular Barrier and the Blood–Brain Barrier, reached brain cells, passed the optical nerves, and transcribed mRNA-Tph2-FLAG in different brain areas. The recombinant Tph2-FLAG was observed in amygdala and brainstem, mainly in raphe dorsal and medial. Relative
Tph2
expression of threefold over basal level was recorded three days after Op-Ad. These results demonstrated that pIRES-hrGFP-Tph2-FLAG, administrated through the eyes was capable of reaching the brain, transcribing, and translating
Tph2
. In conclusion, this study showed the feasibility of delivering therapeutic genes, such as the
Tph2,
the first enzyme, rate-limiting step in the 5-HT biosynthesis.
In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be ...unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia.
91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA).
91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study.
The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.
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