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NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia

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Abstract  

The risk stratification of B-acute lymphoblastic leukemia (B-ALL) is based on clinical and biological factors. However, B-ALL has significant biological and clinical heterogeneity and 50% of B-ALL patients do not have defined prognostic markers. In this sense, the identification of new prognostic biomarkers is necessary. Considering different cohorts of childhood B-ALL patients, gene (DPP4/CD38/ENTPD1/NT5E) and protein (CD38/CD39/CD73) expressions of ectonucleotidases were analyzed in silico and ex vivo and the association with prognosis was established. In univariate analyses, expression of NT5E was significantly associated with worse progression-free survival (PFS) in bone marrow (BM) samples. In multivariate analyses, Kaplan–Meier analysis, and log-rank test, higher NT5E expression predicted unfavorable PFS in BM samples. Considering minimal residual disease (MRD), higher levels of cellularity were associated with the high NT5E expression at day 8 of induction therapy. In addition, we observed that white blood cells (WBC) of childhood B-ALL patients had more CD38 compared to the same cell population of healthy donors (HD). In fact, MRD > 0.1% patients had higher CD38 protein expression on WBC in comparison to HD. Noteworthy, we observed higher CD38 expression on WBC than blasts in MRD > 0.1% patients. We suggest that NT5E gene and CD38 protein expression, of the ectonucleotidases family, could provide interesting prognostic biomarkers for childhood B-ALL.

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Funding

This study was supported by CNPq (PQ no. 302879/2017–0, AMO Battastini grant), FAPERGS (FAPERGS/PQG grant no. 19/2551–0001783-9; ARD grant no. 19/2551–0001269-1 and PRONEX no. 16–2551-0000467–6), and INCT/CNPq/CAPES/ FAPERGS grant no. 465671/2014–4. Fundo de Incentivo a Pesquisa do Hospital de Clínicas de Porto Alegre (project no.: 2018–0401; CAAE no.: 93973218110015327). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)—Finance Code 001.

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Authors and Affiliations

  1. Laboratório de Imunobioquímica do Câncer, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, RS, Porto Alegre, CEP 90035-003, Brazil

    Vitória Brum da Silva Nunes, Camila Kehl Dias, Ana Maria Oliveira Battastini & Fabrício Figueiró

  2. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, RS, Porto Alegre, CEP 90035-003, Brazil

    Vitória Brum da Silva Nunes, Camila Kehl Dias, Marco Antônio De Bastiani, Ana Maria Oliveira Battastini & Fabrício Figueiró

  3. Laboratório de Neuroimagem, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, CEP 90035-003, Brazil

    Marco Antônio De Bastiani

  4. Hospital de Clínicas de Porto Alegre/HCPA, Porto Alegre, RS, CEP 90035-903, Brazil

    Mariela Granero Farias, Fabiane Spagnol, Ana Paula Alegretti, Liane Esteves Daudt, Mariana Bohns Michalowski & Alessandra Aparecida Paz

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  1. Vitória Brum da Silva Nunes
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  2. Camila Kehl Dias
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  3. Marco Antônio De Bastiani
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  4. Mariela Granero Farias
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  8. Mariana Bohns Michalowski
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  9. Ana Maria Oliveira Battastini
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  10. Alessandra Aparecida Paz
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  11. Fabrício Figueiró
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Vitória Brum da Silva Nunes, Camila Kehl Dias, Marco Antônio De Bastiani, and Fabrício Figueiró. The first draft of the manuscript was written by Vitória Brum da Silva Nunes and all authors commented on later versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fabrício Figueiró.

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Ethical approval

The study was conducted in accordance with the 1964 Helsinki Declaration, and the protocol was approved by the Ethics Committee of the Hospital de Clínicas de Porto Alegre (Project number: 2018–0401; CAAE number: 93973218110015327). All guardians of the children provided informed consent.

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da Silva Nunes, V.B., Dias, C.K., De Bastiani, M.A. et al. NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia. Purinergic Signalling 18, 211–222 (2022). https://doi.org/10.1007/s11302-022-09841-x

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