ABSTRACT
OBJECTIVES: Acute lymphoblastic leukemia (ALL) is a clonal disease that accounts for 20% of acute leukemias in adults. A high percentage of adult patients (ranging from 70 to 80%) reach complete remission; however, the 5-year survival rate is only 20-40%. One of the main obstacles to treatment success is the drug resistance of leukemic cells. Therefore, our research group analyzed the ABCB1 and ABCG2 gene expression levels in 61 patients diagnosed with ALL and assessed whether the levels affected the clinical parameters and 40-month survival rate. METHODS: The ABCB1 and ABCG2 gene expression levels were analyzed using real-time polymerase chain reaction in 61 patients diagnosed with ALL and 99 healthy donors as controls. The association between ABCB1 and ABCG2 gene expression levels and clinical variables was determined using the Chi-square test and Fisher's exact test. Overall survival (OS) was determined using the Kaplan-Meier method. RESULTS: The results showed high ABCB1 and ABCG2 gene levels, which were 4.5 and 2.3 times the levels of healthy donors, respectively. A total of 52% of the study patients expressed high ABCB1 levels and were significantly associated with the high-risk patient group and a decreased 40-month survival rate of 78%. Only 49% of the patients expressed high ABCG2 gene levels. No association was found between the clinical parameters and the ABCG2 gene expression levels. CONCLUSIONS: Early detection of ABCB1 gene expression levels could be important for the diagnosis and monitoring of ALL patients.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/biosynthesis , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/biosynthesis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , ATP Binding Cassette Transporter, Subfamily B/biosynthesis , Adolescent , Adult , Disease-Free Survival , Female , Humans , Male , Middle Aged , Survival RateABSTRACT
Acute myeloid leukaemia results from the neoplastic transformation of haematopoietic stem cells. Although advances have been made in its treatment, the mortality rate remains high. As a result, therapeutic alternatives continue to be explored. In this study, we present evidence that suggests that casein, the principal protein in milk, possesses significant antileukaemic properties. We investigated whether casein inhibited the in vitro proliferation and induced the apoptosis of the mouse myelomonocytic leukaemia cell line WEHI-3. By contrast, under identical conditions, casein markedly promotes the proliferation of mouse normal mononuclear bone marrow cells. Since the selective elimination of leukaemia cells is an ideal therapeutic strategy, we also evaluated the antileukaemic potential of casein in vivo. The results showed that casein increases the survival of mice bearing WEHI-3-induced tumours, suggesting that this molecule is also capable of inhibiting the proliferation of these cells in vivo. The evidence that casein inhibited cell proliferation and induced apoptosis in leukaemia cells in vitro, but increased survival in vivo in a leukaemia mouse model, indicates that casein may be useful in leukaemia therapy.
ABSTRACT
This study was conducted to determine the frequency of the most common fusion genes in Mexican pediatric patients with acute lymphoblastic leukemia (ALL). Molecular analysis using RT-PCR was carried out in 53-blood samples: 52 patients with de novo ALL and one with relapsed ALL. The ETV6-RUNX1 fusion was found in 7 cases (13.5%), BCR-ABL fusion was detected in 2 cases (3.8%), and 6 patients (11.5%) expressed the chimeric gene E2A-PBX1. The prevalence of E2A-PBX1 is one of the highest that has been described thus far in childhood ALL. Furthermore, we detected both the BCR-ABL, and E2A-PBX1 fusion in the relapsed patient. With regards to the immunophenotype, ETV6-RUNX1 was expressed in both pre-B and T-cell cases, while the presence of E2A-PBX1 and BCR-ABL was associated with the pre-B ALL phenotype. The prevalence of E2A-PBX1 in Mexican pediatric cases supports the existence of ethnic differences in the frequency of molecular markers of ALL.
Subject(s)
Core Binding Factor Alpha 2 Subunit/genetics , Fusion Proteins, bcr-abl/genetics , Homeodomain Proteins/genetics , Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Proto-Oncogene Proteins c-ets/genetics , Repressor Proteins/genetics , Adolescent , Child , Child, Preschool , Female , Gene Frequency , Humans , Infant , Male , Mexico , Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology , ETS Translocation Variant 6 ProteinABSTRACT
Para conocer los estimulantes mitógenos más adecuados para la iniciación de la actividad mitótica de los blastos se utilizaronultivos de 20 muestras de células de leucemia aguda linfoblástica (LAL). Se analizaron diferentes concentraciones de fitohemaglutinina (PHA), lectina (Phitolacca americana) (FL) y 2-mercaptoetanol (2-ME) mediante la estimulación de cultivos celulares de 20 muestras. La mucoproteina extraída de las plantas (PHA) resultó ser el mejor activador de la mitosis y de la proliferación. A una concentración de 2.5 mg/ml, ocurrió la división celular; en su ausencia, no se observó proliferación celular. Por otra parte, la FL tuvo un efecto menor de la activación de la mitosis en los cultivos; y el 2-ME no presentó efecto alguno sobre la proliferación de estas células. Además, se observó que la acción mitogénica de la PHA implica la activación de la replicación del ADN celular, tal y como lo demostró la incorporación de [3H]-timidina
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Mitogens , Lymphocyte Activation/immunology , Cells, Cultured/ultrastructure , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Hematopoietic System/ultrastructureABSTRACT
The gross structure and the expression of the c-myc oncogene were analyzed in primary cells from 15 acute lymphoblastic leukemia patients. Southern blot analysis was used to detect possible alterations in the structure of this gene. Alterations (rearrangement and/or amplification) were observed in seven of the 15 samples studied. When the expression of MYC protein was evaluated by Western blot analysis, we found no correlation between c-myc gene alterations and p67 c-myc, which was expressed in the 15 samples studied. The analysis of expression also revealed various MYC-related proteins (115, 110 and 60 kD). These proteins were expressed at variable levels in all leukemic cells, other transformed cells, and in normal peripheral blood lymphocytes (PBL) induced to proliferate with interleukin 2. We detected the 110 kD and 40 kD MYC-related proteins in fresh normal PBL and in samples from patients in complete remission. These studies indicate that the c-myc alterations and protein expression are unrelated to percentage of leukemic blasts, cell morphology or immunophenotype. Our work shows that the expression of MYC-related proteins from 115, 60 and 40 kD is associated with mechanisms of cell activation, and perhaps these proteins may play a role in cellular proliferation-transformation.
