Subject(s)
Cytogenetic Analysis , Philadelphia Chromosome , Translocation, Genetic , Adult , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 9 , Fusion Proteins, bcr-abl/genetics , Genetic Variation , Humans , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle AgedABSTRACT
It has been suggested that genetic predisposition to cancer might be related to spontaneous chromosome instability or to fragile site expression. Therefore, spontaneous breakage and fragile sites were analyzed in nine untreated chronic lymphocytic leukemia (CLL) patients to determine their relation to cancer rearrangements. Five cases presented spontaneous gaps and breaks with a random distribution of breakpoints. In cultures treated with fluorodeoxyuridine or aphidicolin, 29 specific bands could be defined as fragile sites. A significant clustering of these sites was found with known common fragile sites (c-fra) and cancer breakpoints described in the literature. Most of these cancer breakpoints were involved in structural abnormalities associated with CLL (p < 0.00001). These data suggest that the expression of specific fragile sites might be related to structural chromosomal aberrations in CLL.
Subject(s)
Chromosome Breakage/genetics , Chromosome Fragility , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Aged , Aphidicolin , Chromosome Fragile Sites , Chromosome Mapping , Female , Floxuridine , Gene Expression Regulation, Neoplastic/drug effects , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Tumor Cells, CulturedABSTRACT
Fifty patients from Argentina with chronic myeloid leukemia (CML) were studied in order to characterize the breakpoint site within the major breakpoint cluster region (M-BCR) and its relationship with the duration of the chronic phase (CP). The DNA digestion with the restriction enzymes: Bgl II, BAM HI and Hind III and hybridization with the 1.2Kb Hind III-Bgl II bcr probe showed that 56% of cases had the breakpoint in 5'M-bcr region and the remaining 44% in 3'M-bcr region. The duration of chronic phase from diagnosis to the onset of the blast crisis (BC) was correlated with the location of the breakpoint within the M-bcr and no statistical differences were observed between the 5' and the 3' groups. These data indicate that the breakpoint site within the bcr gene is not a prognostic indicator of the duration of CP of the disease.
Subject(s)
Chromosome Aberrations , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Philadelphia Chromosome , Adolescent , Adult , Argentina , Blast Crisis , Bone Marrow/pathology , Child, Preschool , Chromosome Banding , Chromosome Mapping , Disease-Free Survival , Female , Humans , Infant , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle AgedABSTRACT
The interferons alpha, beta, and w (IFNA, IFNB, IFNW), are a family of genes that have been mapped on the short arm of chromosome 9 (9p21-22). Deletions of genetic material on 9p are frequently observed in hematological diseases, particularly in lymphoid neoplasias. In this paper we have performed the molecular studies of IFNA and IFNB genes in chronic myeloid leukemia (CML) in order to determine if the deletions of these genes are prevalent in this pathology. Forty CML patients, Philadelphia positive or with BCR/ABL rearrangement, were studied at diagnosis. The analysis of IFNA and IFNB genes was performed by Southern and dot blot techniques. Homozygous or hemizygous deletions of IFNA and IFNB genes could not be detected, indicating that deletions of these genes would not be present or would be a very infrequent event in the chronic phase of the CML patients.