RESUMO
With the combination of immunophenotyping and molecular tests, it is still a challenge to identify the characteristics of T cell acute lymphoblastic leukemia (T-ALL) associated with distinct outcomes. This study tests the possible correlation of cellular expression of CD135 and CD117 with somatic gene mutations in T-ALL. One hundred sixty-two samples were tested, including 143 at diagnosis, 15 from T-lymphoblastic lymphoma at relapse, and four relapse samples from sequential follow-up of T-ALL. CD135 and CD117 monoclonal antibodies were included in the T-ALL panel of flow cytometry. The percentage of cells positivity and the median fluorescence intensity were correlated with gene mutational status. STIL-TAL1, TLX3, FLT3 and IL7R mutations were tested using standard techniques. STIL-TAL1 was found in 24.8%, TLX3 in 12%, IL7R in 10% and FLT3-ITD in 5% of cases. FLT3 and IL7R mutations were mutually exclusive, as were FLT3-ITD and STIL-TAL1. Associations of CD135(high) (p<0.01), CD117(intermediate/high) (p=0.02) and FLT3-ITD, CD117(low) with IL7R(mutated) (p<0.01) and CD135(high) with TLX3(pos) were observed. We conclude that the addition of CD135 and CD117 to the diagnosis can predict molecular aberrations in T-ALL settings, mainly segregating patients with FLT3-ITD, who would benefit from treatment with inhibitors of tyrosine.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Homeodomínio/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptores de Interleucina-7/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Anticorpos Monoclonais , Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Biomarcadores Tumorais/imunologia , Criança , Pré-Escolar , Feminino , Expressão Gênica , Proteínas de Homeodomínio/imunologia , Humanos , Imunofenotipagem , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Masculino , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-kit/imunologia , Receptores de Interleucina-7/imunologia , Recidiva , Proteína 1 de Leucemia Linfocítica Aguda de Células T , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/imunologiaRESUMO
CD26/DPPIV (dipeptidil peptidase IV) displays an array of diverse functional properties, with a role in the development of several human cancers. This enzyme is found mainly anchored in the membrane of cells although it also has an enzymatically active plasma isoform. The regulation of biological activities of cytokines by DPP IV activity has a potential role in the homeostatic regulation of hematopoiesis. In this study, we analyzed the CD26 antigen cell membrane expression by flow cytometry and the DPPIV activity in plasma of patients of acute leukemia. The results showed that the plasma DPPIV activity is significantly higher in leukemia patients and could be 100% inhibited by Januvia (Merck Sharp & Dohme) a selective DPPIV inhibitor. Although CD26 expression on immune cells were not leukemia-dependent the analysis of the correlation between CD26 expression and the DPPIV plasma activity were statistically significant (p < 0.01) in acute lymphoid leukemia (B-ALL and T-ALL).