ABSTRACT
BACKGROUND: Despite the advances in the cure rate for acute myeloid leukemia (AML), a considerable number of patients die from the disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins, such as P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP), confers resistance to the treatment of these leukemias. METHODS: To analyze the expression of the Pgp and MRP1 in patients with AML and determine their correlation between expression and demographic, clinical, and laboratorial variables, bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by flow cytometry. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in children, while also observing a high incidence in patients with refractory, recurrence, and secondary disease in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed an association between the expression of Pgp and MRP1 and CD34, CD7, and also M7, M5a, and M2-AML of French-American-British classification. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis of patients with AML.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Multidrug Resistance-Associated Proteins/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Biomarkers, Tumor , Child , Child, Preschool , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Female , Flow Cytometry , Humans , Immunophenotyping , Infant , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Multidrug Resistance-Associated Proteins/metabolism , Phenotype , Prognosis , Symptom Assessment , Young AdultABSTRACT
BACKGROUND: Although more than 14 loci may be involved in the development of nonsyndromic cleft lip and palate (NSCLP), the etiology has not been fully elucidated due to genetic and environmental risk factor interactions. Despite advances in identifying genes associated with the NSCLP development using traditional genetic mapping strategies of candidate genes, genome-wide studies, and epidemiologic and linkage analysis, microarray techniques have become important complementary tools in the search for potential causative oral clefts genes in genetic studies. Microarray hybridization enables scanning of the whole genome and detecting copy number variants (CNVs). Although common benign CNVs are often smaller, with sizes smaller than 20 kb, here we reveal small exonic CNVs based on the importance of the encompassed genes in cleft lip and palate phenotype. METHODS: Microarray hybridization analysis was performed in 15 individuals with NSCLP. RESULTS: We identified 11 exonic CNVs affecting at least one exon of the candidate genes. Thirteen candidate genes (COL11A1-1p21; IRF6-1q32.3; MSX1-4p16.2; TERT-5p15.33; MIR4457-5p15.33; CLPTM1L-5p15.33; ESR1-6q25.1; GLI3-7p13; FGFR-8p11.23; TBX1-22q11.21; OFD-Xp22; PHF8-Xp11.22; and FLNA-Xq28) overlapped with the CNVs identified. CONCLUSIONS: Considering the importance to NSCLP, the microdeletions that encompass MSX1, microduplications over TERT, MIR4457, CLPTM1L, and microduplication of PHF8 have been identified as small CNVs related to sequence variants associated with oral clefts susceptibility. Our findings represent a preliminary study on the clinical significance of small CNVs and their relationship with genes implicated in NSCLP.
ABSTRACT
BACKGROUND: A functional variant in the MDM2 promoter (a T/G substitution, SNP309) was found to be associated with increased expression of MDM2 gene products and at significantly earlier age onset of tumors in both hereditary Li-Fraumeni individuals and sporadic cancer patients. We tested the hypothesis that this functional variant was associated with either risk or early age diagnosis of cervical cancer in a Brazilian population. METHODS: A primer-introduced restriction analysis PCR assay was used to genotype the MDM2 SNP309 of 72 cervical carcinoma patients and 100 healthy women. RESULTS: No statistically significant association was observed between SNP309 and cervical cancer. We did not find allele or genotype frequency differences between the group of patients with cancer diagnosis at an early age (younger than 40 years old) and the group of older patients. CONCLUSIONS: Our findings suggest that SNP309 MDM2 may not be a risk factor for cervical cancer.
