RESUMO
AIM: CD44v6 is an isoform of CD44 that can be present in soluble form (sCD44v6). The aim of this study is to evaluate the presence of soluble CD44 (sCD44) and sCD44v6 in serum of children with B-cell precursor acute lymphoblastic leukemia (B-ALL) and their relationship with prognosis. METHODS: sCD44v6 and sCD44 levels were measured in the sera of patients and healthy children by enzyme-linked immunosorbent assay. The level of the molecules was analyzed in relation to laboratory and clinical characteristics of the patients at presentation and response to therapy. RESULT: sCD44v6 was significantly lower in patients (103.4 ± 44 ng/mL) than in controls (173.5 ± 73.6 ng/mL) whereas the serum level of sCD44 showed no significant difference between the groups. In patients, sCD44v6 quantity was inversely correlated with sCD44 level (r = -0.57, P < 0.01). The mean serum level of sCD44 in patients with >20% positivity for CD44 surface expression was greater than that in patients with ≤20% positivity (1345 ± 409 ng/mL vs 1111 ± 390 ng/mL, P = 0.05). sCD44v6 showed no significant association with response to therapy and prognostic factors except the TEL/AML1 positivity, as it was higher in TEL/AML1 positive patients (157.3 ± 55.6 ng/mL) than negative ones (92 ± 43.6 ng/mL, P = 0.036). Conversely, sCD44 was lower in TEL/AML1 positive patients and showed a significant association with white blood cell number, blast percentage and extramedullary involvement. CONCLUSION: The lower level of sCD44v6 in patients than in controls suggests the possible diagnostic value of this molecule for B-ALL. The presence of an association with established prognostic factors despite of no relationship with disease outcome suggested these molecules for more studies in larger patient cohorts.
Assuntos
Receptores de Hialuronatos/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Adolescente , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/análise , Feminino , Humanos , Lactente , Masculino , Proteínas de Fusão Oncogênica/análise , PrognósticoRESUMO
Fas molecule is one of the main important molecules involved in apoptotic cell death. Single nucleotide polymorphisms in the promoter of Fas gene at positions -1377G/A and -670 A/G may affect its expression and play an important role in the pathology of leukemia. In the present study the association between these polymorphisms and risk of the development of acute lymphoblastic leukemia (ALL) in children with ALL compared to cancer-free control subjects was examined by polymerase chain reaction- based restriction fragment length polymorphism. The relationship between the polymorphisms and clinical and laboratory features of the patients and response to therapy were determined. No significant differences in genotype and allele frequencies between the patients and the control subjects at positions -670 and -1377 were detected. Evaluation of the prognostic factors revealed an association between the GG genotype at position -670 and liver involvement in ALL patients (p < 0.04). Although patients with -1377 AA genotype showed shorter mean complete remission duration, the result of survival analysis did not reach to be significant. In conclusion, results of this study showed no contribution of Fas genotypes at positions -670 and -1377 to risk of ALL in children. The association of Fas GG genotype at position -670 with liver involvement in the patients may show its important role in prognosis of ALL.
Assuntos
Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptor fas/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Lactente , Masculino , Polimorfismo de Fragmento de Restrição/genética , Prognóstico , Fatores de RiscoRESUMO
The expression of CD44 and CD27 molecules correlates with the differentiation stage of B cell precursors. The present study was designed to investigate the prognostic relevance of CD44 and CD27 molecules in patients with B cell acute lymphoblastic leukemia (ALL). CD27 and CD44 expression was determined in 58 patients by flow cytometry and their relation to established prognostic factors and response to therapy was investigated. Four patterns of expression were found; CD27 single positive (SP) in 20.7 % of patients, CD44SP in 25.8 %, CD27CD44 double positive (DP) in 20.7 %, and CD27CD44 double negative (DN) in 32.8 %. CD27 expression and the CD27SP pattern correlated directly with TEL/AML1 genotype (P = 0.012). Conversely, CD44 expression and the CD44SP pattern correlated inversely with this genotype (P = 0.016). Patients with the DP pattern had a lower WBC count (P = 0.03), lower percentage of blasts in their bone marrow (P = 0.028), and higher platelet count, whereas CD44SP patients had a higher WBC count and higher percentage of bone marrow blasts. Moreover, a negative association between DN pattern and complete remission (CR) rate was detected (P = 0.03). Mean CD27 expression was significantly higher in low-risk group and in patients who achieved CR (P = 0.001), and in those with a higher platelet number (P = 0.046) and less extramedullary involvement (P = 0.008). Although survival and CR duration were longer in patients with DP pattern and shorter in those with DN pattern, the result did not reach statistical significance. The expression of CD27 together with CD44 showed a relationship with several established risk factors as well as response to therapy, indicating the biological significance of these molecules in ALL.
