RESUMO
BACKGROUND: The current predictor of the Chronic myeloid leukemia (CML) patients' outcome is the degree of response to targeted therapy; here we search for a biomarker predicting CML outcome before start of therapy. This study aimed to assess the impact of the CD34+/CD38- stem cells (SCs) burden in chronic myeloid leukemia (CML) on treatment response and patients' outcomes. METHODS: Our study included 65 CML patients in the chronic phase. The patients' CD34+/CD38- stem cells were quantified using flowcytometry before and after treatment by frontline imatinib (IM) therapy. The median follow-up for all patients was 18 months. RESULTS: CD34+/CD38- stem cells frequency at diagnosis and after therapies are correlated to known prognostic markers (blast cells count, spleen size, total White cell count, and clinical scores). After therapy, the leukemic stem cells count dropped rapidly. The pretreatment CD34+/CD38- stem cells burden predicts response to frontline therapy. In addition, high SCs frequency at diagnosis predicts poor molecular response, transformation to AML, and poor patients' outcomes. CONCLUSION: The percentage of CD34+/CD38- SCs burden at diagnosis reflects the CML disease behavior and is considered a biomarker for predicting CML patients' response to first-line Tyrosine kinase inhibitors (TKI) therapy.
Assuntos
ADP-Ribosil Ciclase 1 , Antígenos CD34 , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Transformação Celular Neoplásica/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
The present study assessed protein and gene expression levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), and MMP-9 in urine and blood samples of 50 patients with bladder carcinoma. The expression of TIMP-2, MMP-2, and MMP-9 levels with tumor stage and grade was also assessed. Results showed that the expression levels of MMP-2 and MMP-9 in both blood and urine were significantly elevated in group 1 when compared with groups 2 and 3 healthy subjects. The discriminatory ability in the diagnosis of bladder carcinoma of MMP-2 and MMP-9 expression was confirmed by receiver operating characteristic curve analysis that revealed a sensitivity and specificity of 100%. MMP-2 and MMP-9 levels were not correlated with grade or stage of the tumor. With respect to TIMP-2 blood and urine levels, results showed a significant decrease in gene expression levels in bladder carcinoma group, whereas, TIMP-2 protein showed a significant increase in bladder carcinoma.
