RESUMEN
IKZF1 gene located in 7p12 of chromosome, and Ikaros family zinc finger encoded by IKZF1, are lymphoid-restricted transcription factors. In recent years, it has been demonstrated that the mutation of IKZF1 gene involved in proliferation, metastasis and prognosis of many malignant tumor except acute lymphoblastic leukemia, and also involved in complex phenotypes and susceptibility to systemic lupus erythematosus. This review briefly introduces the molecular structure and physiological function of Ikaros, focusing on its function and molecular mechanism in proliferation, metastasis and prognosis of malignant tumors, and its role in the systemic lupus erythematosus.
Asunto(s)
Lupus Eritematoso Sistémico , Neoplasias , Humanos , Factor de Transcripción Ikaros , PronósticoRESUMEN
Molecular markers have become an invaluable tool in monitoring disease status particularly of leukemias, as bone marrow samples can be easily collected for analysis during all stages of disease development including diagnosis, treatment, and follow-up. Two genes that have been used as prognostic markers in acute leukemia are Wilms' tumor (WT1) and multidrug resistance-1 (MDR1). A novel gene, epidermal growth factor receptor pathway substrate 8 (EPS8), is often over-expressed and associated with poor outcome in some solid tumor types. However, whether EPS8 is also associated with the development of acute lymphoblastic leukemia (ALL) is unclear. Here, quantitative real-time PCR was used to evaluate the expression of EPS8, MDR1, and WT1 in bone marrow samples of adult ALL patients (n=107) and non-leukemia controls (n=22). EPS8, MDR1, and WT1 were detected in ALL patients, and significant correlations were found between expression profiles for EPS8 and MDR1, EPS8 and WT1, and MDR1 and WT1. In general, high expression of EPS8, MDR1, or WT1 in patients was associated with a higher risk of relapse. Furthermore, when patients were stratified based on high or low expression of the genes, Kaplan-Meier survival analysis indicated that disease-free survival of patients with the high-EPS8/high-WT1/high-MDR1 profile was significantly shorter than in patients with the low-EPS8/low-WT1/low-MDR1 profile or those excluded from either of these groups (P<0.0001). Thus, EPS8, as MDR1 and WT1, may be a clinically valuable biomarker for assessing the outcome of ALL patients.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Biomarcadores de Tumor/biosíntesis , Médula Ósea/metabolismo , Regulación Leucémica de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Subfamilia B de Transportador de Casetes de Unión a ATP/biosíntesis , Adolescente , Adulto , Anciano , Médula Ósea/patología , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Tasa de Supervivencia , Proteínas WT1/biosíntesisRESUMEN
In recent years, standardized treatment based on the risk stratification has been applied to clinical diagnosis and treatment of leukemia, which significantly improves the remission rate of ALL. However, relapse after remission remains an important challenge for long term efficacy. Chromosomal karyotype analysis is often used clinically to study the genetic features of ALL. As leukemia-specific markers, the cytogenetic and molecular genetic abnormalities can be used to evaluate prognosis and make an effective and optimal therapy. Furthermore, they are also used to track minimal residual disease. Therefore, the cytogenetic and molecular genetic abnormalities may become a monitor and a new target for the treatment of leukemia. This review briefly introduces the structure and physiological function of B-ALL associated cytogenetic and molecular genetic abnormalities, focusing on their prognostic effect on B-ALL.