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: Hereditary hemochromatosis (HH) is a genetic disease caused by the high absorption and deposition of iron in several organs. This accumulation results in several clinical complications such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders, and skin darkening. The H63D and C282Y mutations are well defined in the HH etiology. The objective of this article is identification of the H63D and C282Y mutations in the HFE protein gene and the frequency assessment of these mutations in patients with persistent increase of serum ferritin in patients from Natal City from state of Rio Grande do Norte, located in northeastern Brazil. RESULTS: Of the 299 patients studied for C282Y and H63D, 48.49% showed absence of mutation and 51.51% showed some sort of mutation: heterozygous C282Y mutation in 4.35% patients, homozygous C282Y mutation in 2.67% patients, heterozygous H63D mutation in 31.44% patients, homozygous H63D mutation in 8.03% patients, and heterozygous for the mutation in both genes (C282Y/H63D) in 5.02% patients. The S65C mutation was studied in 112 patients and heterozygous mutation (S65D/WT) in 2.67% of patients and double mutation (H63D/S65C) in 1.78% of patients were observed. CONCLUSION: Due to the high prevalence of hemochromatosis, its genetic diagnosis has become a challenge, especially in the high-risk group.
