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  1. Article ; Online: Altered Arylamine N-acetyltransferase 1 and miR-1290 Levels in Childhood Acute Lymphoblastic Leukemia: A Pilot Study.

    Hernandez-Gonzalez, Oswaldo / Del Carmen Milan-Segovia, Rosa / Zavala-Reyes, Daniel / Alvarado-Zamarripa, Dinora Margarita / Ortiz-Zamudio, Juan Jose / Correa-Gonzalez, Lourdes Cecilia / Vargas-Morales, Juan Manuel / Uresti-Rivera, Edith Elena / Portales-Perez, Diana Patricia

    In vivo (Athens, Greece)

    2023  Volume 37, Issue 3, Page(s) 1129–1144

    Abstract: Background/aim: Arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) are drug-metabolizing enzymes that play a key role in the development of acute lymphoblastic leukemia (ALL).: Materials and methods: This study evaluated NAT1 and NAT2 mRNA and ... ...

    Abstract Background/aim: Arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) are drug-metabolizing enzymes that play a key role in the development of acute lymphoblastic leukemia (ALL).
    Materials and methods: This study evaluated NAT1 and NAT2 mRNA and protein expression and their enzymatic activity in peripheral blood mononuclear cells (PBMC) from patients with ALL (n=20) and healthy children (n=19) and explored the mechanisms that regulate these enzymes in ALL such as microRNAs (miR-1290, miR-26b) and SNPs.
    Results: PBMC from patients with ALL showed a decrease in NAT1 mRNA and protein expression. In addition, NAT1 enzymatic activity was decreased in patients with ALL. There was no influence of SNP 559 C>T or 560 G>A on low NAT1 activity. The lower expression of NAT1 might be related to the loss of acetylated histone H3K14 in the NAT1 gene promoter in patients with ALL and the higher relative expression of miR-1290 in the plasma of patients with relapsed ALL compared with healthy controls. There were significantly fewer CD3+/NAT1+ double-positive cells in patients who relapsed compared with control subjects. Based on a t-distributed stochastic neighbor embedding algorithm, CD19+ cells that reappeared in patients with relapse showed low NAT1 expression. In contrast, for NAT2, there were no significant results.
    Conclusion: The expression and function of NAT1 and miR-1290 levels could be involved in modulating immune cells altered in ALL.
    MeSH term(s) Child ; Humans ; Leukocytes, Mononuclear/metabolism ; Pilot Projects ; Arylamine N-Acetyltransferase/genetics ; Arylamine N-Acetyltransferase/metabolism ; MicroRNAs/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; RNA, Messenger
    Chemical Substances N-acetyltransferase 1 (EC 2.3.1.5) ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; MicroRNAs ; RNA, Messenger ; NAT2 protein, human (EC 2.3.1.5) ; MIRN1290 microRNA, human
    Language English
    Publishing date 2023-04-27
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 807031-3
    ISSN 1791-7549 ; 0258-851X
    ISSN (online) 1791-7549
    ISSN 0258-851X
    DOI 10.21873/invivo.13188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Population pharmacokinetics of methotrexate in Mexican pediatric patients with acute lymphoblastic leukemia.

    Medellin-Garibay, Susanna E / Hernández-Villa, Nadia / Correa-González, Lourdes Cecilia / Morales-Barragán, Miriam Nayeli / Valero-Rivera, Karla Paulina / Reséndiz-Galván, Juan Eduardo / Ortiz-Zamudio, Juan José / Milán-Segovia, Rosa Del Carmen / Romano-Moreno, Silvia

    Cancer chemotherapy and pharmacology

    2019  Volume 85, Issue 1, Page(s) 21–31

    Abstract: Purpose: To develop and validate a population pharmacokinetic model of Methotrexate (MTX) in Mexican children with acute lymphoblastic leukemia (ALL) for the design of personalized dosage regimens based on the anthropometric and physiological ... ...

    Abstract Purpose: To develop and validate a population pharmacokinetic model of Methotrexate (MTX) in Mexican children with acute lymphoblastic leukemia (ALL) for the design of personalized dosage regimens based on the anthropometric and physiological characteristics of each patient.
    Methods: A prospective study was developed in 50 children (1-15 years old) with ALL diagnosis attended at Pediatric Hemato-Oncology Service from Hospital Central "Dr. Ignacio Morones Prieto" and under treatment with high doses of MTX administered in 24-h continuous intravenous infusion. Plasma concentrations of MTX were determined in blood samples collected at 24, 36, 42 or 48 h post-infusion, by means of the CMIA immunoassay. The development of the population pharmacokinetic model was performed using the NONMEM
    Results: A two-compartment open model was selected to describe concentration-time data and body surface area (BSA) was the covariate that influences on MTX total CL. The population pharmacokinetic model obtained was: CL (L/h) = 6.5 × BSA
    Conclusions: The establishment of MTX dosing criteria in children with ALL should be adjusted based on the BSA of each patient to optimize oncological therapy and reduce the development of adverse effects. Therapeutic drug monitoring is an essential tool to individualize MTX doses to reduce toxicity and improve patients' outcomes.
    MeSH term(s) Adolescent ; Antimetabolites, Antineoplastic/pharmacokinetics ; Antimetabolites, Antineoplastic/therapeutic use ; Body Surface Area ; Child ; Child, Preschool ; Drug Monitoring ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Methotrexate/pharmacokinetics ; Methotrexate/therapeutic use ; Mexico/epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Prognosis ; Prospective Studies ; Tissue Distribution
    Chemical Substances Antimetabolites, Antineoplastic ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2019-10-31
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-019-03977-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Genetic polymorphisms of arylamine N-acetyltransferases 1 and 2 and the likelihood of developing pediatric acute lymphoblastic leukemia.

    Hernández-González, Oswaldo / Ortiz-Zamudio, Juan José / Rodríguez-Pinal, Cristian Jazmín / Alvarado-Morales, Ildemar / Martínez-Jiménez, Verónica Del Carmen / Salazar-González, Raúl Alejandro / Correa-González, Lourdes Cecilia / Gómez, Rocío / Portales-Pérez, Diana Patricia / Milán-Segovia, Rosa Del Carmen

    Leukemia & lymphoma

    2017  Volume 59, Issue 8, Page(s) 1968–1975

    Abstract: Acute lymphoblastic leukemia (ALL) is one of the main causes of death in children and is associated with both genetic susceptibility and environmental factors. Genes encoding the arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) isoenzymes are ... ...

    Abstract Acute lymphoblastic leukemia (ALL) is one of the main causes of death in children and is associated with both genetic susceptibility and environmental factors. Genes encoding the arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) isoenzymes are highly polymorphic among populations. Single-nucleotide polymorphism analysis was performed by real-time polymerase chain reaction from the genomic DNA of 225 healthy subjects and 57 children with ALL diagnoses. Significant associations were found between the development of ALL and the presence of the haplotypes NAT1*3 (Odds ratio [OR], 2.1), NAT1*4 (OR, 1.92), NAT2*6B (OR, 3.30), NAT2*6J (OR, 3.25) and NAT2*7A (OR, 2.45) and the NAT1 rapid (OR, 6.69) and NAT2 slow phenotypes (OR, 2.95). Our results indicate that haplotypes that provide rapid NAT1 and slow NAT2 acetylating phenotypes may influence the development of ALL in children.
    MeSH term(s) Adolescent ; Adult ; Aged ; Arylamine N-Acetyltransferase/genetics ; Child ; Child, Preschool ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Genotype ; Haplotypes ; Humans ; Infant ; Isoenzymes/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Young Adult
    Chemical Substances Isoenzymes ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; N-acetyltransferase 1 (EC 2.3.1.5) ; NAT2 protein, human (EC 2.3.1.5)
    Language English
    Publishing date 2017-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2017.1406090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Valor pronóstico del inmunofenotipo en la respuesta temprana de la leucemia aguda linfoblástica pre-B en niños.

    Correa-González, Lourdes Cecilia / Mandeville, Peter B / Manrique-Dueñas, Javier / Alejo-González, Francisco / Salazar-Martínez, Abel / de Pérez-Ramírez, Oscar Jesús / Hernández-Sierra, Juan Francisco

    Gaceta medica de Mexico

    2005  Volume 141, Issue 6, Page(s) 477–482

    Abstract: Objective: To determine the prognostic value of preB immunophenotype and its variants on early treatment response among of acute pediatric lymphoblast leukemia.: Patients and methods: A case-control study nested in a cohort was carried out with male ... ...

    Title translation Prognostic value of pre-B immunophenotype in early treatment response among acute pediatric lymphoblast leukemia patients.
    Abstract Objective: To determine the prognostic value of preB immunophenotype and its variants on early treatment response among of acute pediatric lymphoblast leukemia.
    Patients and methods: A case-control study nested in a cohort was carried out with male and female patients 15 years and younger with recently diagnosed pre-B lymphoblast leukemia. A panel of B, T, monoclonal antibodies of the myelo-monocytic and megakaryocytic cell type was used. Response was assessed by bone marrow aspiration 14 days post treatment.
    Results: 54 patients were included. The median age was 7 years (2 months - 14 years) median leukocyte count was 13,450/mm3 (1200-986,000/mm3). We identified 29 cases with late pre-B immune phenotype, 19 cases with common pre B and 6 cases with early preB immunophenotype. Eleven, patients also displayed myeloid antigens. A significant association (p=0.034) was found between early treatment response and the presence of myeloid antigens. No association was found between the pre-B immunophenotype, age and leukocyte count with early treatment response (p=0.264).
    Conclusions: We need to pay special emphasis on early treatment response in children with lymphoblast leukemia as our study did not corroborate the common finding that clinical factors and immune phenotype can be predictive factors.
    MeSH term(s) Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Immunophenotyping ; Infant ; Leukemia, Lymphoid/drug therapy ; Leukemia, Lymphoid/immunology ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Prognosis
    Language Spanish
    Publishing date 2005-11
    Publishing country Mexico
    Document type English Abstract ; Journal Article
    ZDB-ID 425456-9
    ISSN 0016-3813
    ISSN 0016-3813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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