Tissue and organ differentiation is tightly controlled to ensure proper development and function of the growing embryo as well as cells such as lymphocytes that differentiate throughout the adult stage. Therefore it is vital that the genes and the protein they encode that are involved in these processes function accurately. Hence, any mutation or error that occurs along the way can result in extensive damage, which is expressed in various ways in the embryo and can result in immune pathogenesis, including immunodeficiency and autoimmune diseases, when lymphocyte development is altered. A number of studies have been carried out to look at the genes regulating transcription in tissue differentiation, including the transcription factors Pbx1. This gene is of particular interest to us as we have identified that it is associated with systemic lupus erythematosus susceptibility (Cuda et al., in press). This perspective summarizes the known roles of Pbx1 in tissue differentiation as well as our recent findings associating genetic variations in Pbx1 to lupus susceptibility, and we will speculate on how this gene controls the maintenance of immune tolerance in T cells.
Animals ; Cell Differentiation ; Chromatin Immunoprecipitation ; DNA-Binding Proteins ; genetics ; immunology ; Genetic Loci ; immunology ; Genetic Predisposition to Disease ; Homeodomain Proteins ; genetics ; immunology ; Humans ; Immune Tolerance ; Lupus Erythematosus, Systemic ; genetics ; immunology ; Lymphocyte Activation ; Mice ; Mice, Transgenic ; Pre-B-Cell Leukemia Transcription Factor 1 ; Protein Structure, Tertiary ; Proto-Oncogene Proteins ; genetics ; immunology ; Signal Transduction ; T-Lymphocytes, Regulatory ; cytology ; immunology ; Transcription Factors ; genetics ; immunology ; Tretinoin ; metabolism

Animals ; DNA-Binding Proteins ; genetics ; immunology ; Genetic Loci ; immunology ; Genetic Predisposition to Disease ; Homeodomain Proteins ; genetics ; immunology ; Humans ; Lupus Erythematosus, Systemic ; genetics ; immunology ; Lymphocyte Activation ; Mice ; Mice, Transgenic ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins ; genetics ; immunology ; T-Lymphocytes, Regulatory ; cytology ; immunology ; Transcription Factors ; genetics ; immunology

<b>OBJECTIVEb>In childhood acute lymphoblastic leukemia (ALL), cytogenetics plays an important role in diagnosis, allocation of treatment and prognosis. On the basis of the conventional cytogenetic analysis, molecular methods have improved pediatric hematologists/oncologist's ability to accurately and rapidly perform risk-stratification on patients with childhood ALL during the last few years. The aim of the present study was to assess the demography of cytogenetic abnormalities in childhood ALL.

<b>METHODb>The study subjects consisted of 124 newly diagnosed ALL patients younger than 16 years of age, who were diagnosed at the Department of Pediatric Hematology/Oncology, Soochow University Children's Hospital. The diagnosis and FAB subtypes of ALL was determined by Wright-Giemsa-stained bone marrow smears and cytochemical staining. Immunophenotyping of the bone marrow samples was performed by flow cytometry. Multiplex polymerase chain reaction (Multiplex PCR) analysis was performed to detect the 29 most common leukemia translocations for routine molecular diagnostic hematopathology practice, and complement the information gained from conventional cytogenetic analysis.

<b>RESULTSb>Cytogenetic analysis was successful in 112 of 124 children with ALL. Sixty-eight (60%) of them had clonal chromosomal abnormalities. Numerical imbalances consisted of hyperdiploid (> 47 chromosomes, 36 cases), hypodiploid (< 46 chromosomes, 14 cases), pseudodiploidy (18 cases). Chromosomal translocations were observed in 13 patients by conventional cytogenetic analysis. Three cases were found positive for 4; 11 translocation, 3 cases for 9; 22 translocation, 1 case for 1; 19 translocation and 6 cases for other rare translocations. Multiplex-PCR analysis detected 116 of the 124 ALL patients. Thirteen cases of TEL-AML1, 10 cases of rearrangement in the MLL gene, 4 cases of E2A-PBX1, 4 cases of E2A-HLF, 3 cases of BCR-ABL, 2 cases of TLS-ERG, 32 cases of HOX11 were detected by Multiplex PCR in B-lineage leukemias. SIL-TAL1 had been found in 4 of 7 of T-lineage leukemias.

<b>CONCLUSIONSb>Sixty-eight cases of ALL showed chromosomal aberrations. Multiplex PCR positivity was detected in 59 (50%) of the 116 ALL patients studied. Multiplex PCR combined with chromosomal analysis uncovered chromosomal abnormalities in 95 of 124 (77%) of ALL patients and supplemented each other in detecting chromosomal abnormalities.

Adolescent ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Child ; Child, Preschool ; Chromosome Aberrations ; Core Binding Factor Alpha 2 Subunit ; genetics ; Cytogenetic Analysis ; DNA-Binding Proteins ; genetics ; Female ; Fusion Proteins, bcr-abl ; genetics ; Gene Fusion ; genetics ; Homeodomain Proteins ; Humans ; Immunophenotyping ; methods ; Infant ; Karyotyping ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Pre-B-Cell Leukemia Transcription Factor 1 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Proto-Oncogene Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Translocation, Genetic

<b>OBJECTIVEb>To apply linkage disequilibrium (LD) maps to associations studies with high throughput single nucleotide polymorphisms (SNPs).

<b>METHODSb>Seven hundred and fifty-four SNPs were genotyped in 160 Shanghai Chinese. LD maps were constructed in cases and controls separately. By comparing the decline of LD unit with distance between the two groups, disease susceptible loci were estimated. This method was compared with traditional analyses including LD analysis, single SNP and haplotype analyses.

<b>RESULTSb>The analysis of LD maps could detect the chromosome regions with different LD patterns between the cases and controls. The alleles and/or haplotypes frequencies of SNPs within the regions had significantly different distributions or trends of significantly different distributions.

<b>CONCLUSIONb>This method may be applied to analyze the data from association studies with high throughput SNPs genotype information.

Adult ; Aged ; Case-Control Studies ; DNA-Binding Proteins ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Gene Frequency ; Genome-Wide Association Study ; methods ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins ; genetics ; Retinoid X Receptor gamma ; genetics