Low brain-derived neurotrophic factor levels are associated with active disease and poor prognosis in childhood acute leukemia

Article type: Research Article

Authors: Portich, Júlia Plentz^{a; b; 1} | Gil, Mirela Severo^{a; b; 1} | dos Santos, Rafael Pereira^{a; b; c} | Goulart, Bruno Kilpp^d | Ferreira, Maria Beatriz Cardoso^b | Loss, Jiseh Fagundes^e | Gregianin, Lauro José^{e; f} | Brunetto, Algemir Lunardi^c | Brunetto, André Tesainer^c | Roesler, Rafael^{a; b} | de Farias, Caroline Brunetto^{a; c; *}

Affiliations: [a] Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil | [b] Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil | [c] Children's Cancer Institute, Porto Alegre, RS, Brazil | [d] Medical Laboratory, Parque Belém Hospital, Porto Alegre, RS, Brazil | [e] Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil | [f] Department of Pediatrics, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

Correspondence: [*] Corresponding author: Caroline Brunetto de Farias, Children's Cancer Institute and Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil. Tel.: +55 51 33597616; Fax: +55 51 33598012; E-mail:[email protected],[email protected]

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related receptor kinase B (TrkB) are involved in the maturation of B lymphocytes in the bone marrow (BM), promote cell differentiation in B-cell malignancies, and are associated with poor prognosis in adults with acute leukemia (AL). However, the role of BDNF in pediatric AL remains poorly understood. OBJECTIVE: We carried out a cohort observational study to evaluate BDNF levels in BM or peripheral blood (PB) samples from children with AL. METHODS: BM or PB samples were collected from 57 children and adolescents with acute lymphoid leukemia (ALL), 14 children and adolescents with acute myeloid leukemia (AML), and 44 healthy individuals (HI) of the same age range. RESULTS: BDNF levels at diagnosis in AL patients were significantly lower when compared to HI. Samples from patients in complete remission from disease had higher levels of BDNF compared to those obtained from patients with malignant cells. Moreover, BDNF levels at diagnosis in patients who died were significantly lower compared to those found in survivors. CONCLUSIONS: These findings provide the first evidence for a possible role of BDNF as a marker of active disease and poor prognosis in pediatric AL.

Keywords: Brain-derived neurotrophic factor, neurotrophin, acute lymphoid leukemia, acute myeloid leukemia

DOI: 10.3233/CBM-160646

Journal: Cancer Biomarkers, vol. 17, no. 3, pp. 347-352, 2016