OBJECTIVETo identify the ETV6 gene rearrangement in patients with myelodysplastic syndromes (MDS) and explore its relationship with prognosis and disease stages.

METHODSETV6 rearrangement in 58 MDS cases were detected by conventional cytogenetics and Split-signal FISH. RT-PCR was used to detect 9p24-12p13 balance translocation with special designed primers ETV6F1/F2 and JAK2R1/R2. The relationship between ETV6 rearrangement and prognosis and disease staging in MDS patients was analyzed.

RESULTSETV6 rearrangement were found in 4 (6.9%) of 58 cases, among which ETV6/JAK2 fusion was identified by RT-PCR in 1 (1.7%) case. The mean follow-up duration was 12 months. All 4 patients (100%) with rearrangement transformed into acute leukemia, with a median survival time (MS) of 7 months; while 10 patients (17%) in the non-translocation group transformed to acute leukemia, with a MS of 28 months. In addition, all 4 patients (100%) with rearrangement were in advanced stage of MDS( RAEB), while 17 cases (31.5%) in non-rearrangement group were in that stage.

CONCLUSIONSETV6 rearrangement has higher expression rate (6.9%), and is closely associated with disease stage and prognosis in MDS.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; pathology ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins c-ets ; genetics ; Repressor Proteins ; genetics

AIM AND METHODSTo investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) in the regulation of cells proliferation, the expression of MKP-1 and extracellular signal-regulated kinase-1 (ERK-1) in heart and aorta of spontaneous hypertensive rat (SHR) and WKY were studied. We also investigated the effect of MKP-1 genes,which were transfected into vascular smooth muscle cells (VSMC) using the classical calcium phosphate coprecipitation technique, on the incorporation of 3H-TdR in VSMC stimulated by angiotensin II (Ang II).

RESULTS(1) Compared with that of WKY, MKP-1 expression in heart and aorta were significantly decreased by 53% (P < 0.01) and 45% (P < 0.01) in SHR, respectively. While the expression of ERK-1 in heart and aorta of SHR were higher than that of WKY (P < 0.01). The ratio of ERK-1/MKP-1 in heart and aorta of SHR were significantly higher than that of WKY. (2) 3H-TdR incorporation in VSMC stimulated by Ang II (10(-7) mol/L) was increased by 207% (P < 0.01), compared with control group. In the transfected cells with wild MKP-1 gene, Ang II-induced incorporation of 3H-TdR lowered 63%, compared with untransfected cells (P < 0.05). There were no marked inhibitive role between mutant MKP-1-transfected cells and blank vector-transfected cells in response to Ang II, compared with Ang II group (P > 0.05).

CONCLUSIONThese results showed that the expression of ERK-1 in heart and aorta isolated from SHR, which stimulated proliferation and hypertrophy of cells, is higher than that of MKP-1 which dephosphorylates and inactivated ERK-1. In addition, MKP-1 significantly inhibits Ang II-stimulated proliferation of VSMC.

Angiotensin II ; pharmacology ; Animals ; Aorta ; cytology ; enzymology ; Cell Proliferation ; Cells, Cultured ; Dual Specificity Phosphatase 1 ; metabolism ; Heart ; Hypertension ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Muscle, Smooth, Vascular ; cytology ; Myocardium ; cytology ; enzymology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo evaluate the potential usefulness of a multivariable model in predicting the response to immunosuppressive therapy (IST) in patients with aplastic anemia (AA), and its application to the clinical practice.

METHODSPB T cells subpopulation and BM T cells intracellular IFN-gamma and IL-4 were serially analyzed by flow cytometry (FCM) before and during treatment. HLA-DRB1 * 1501 phenotype was analyzed by PCR-SSP. The predictive potentials of different parameter combinations for clinical responsiveness were statistically assessed.

RESULTSIn all evaluated parameters, CD8+ cell intracellular IFN-gamma had the relatively best diagnostic value with sensitivity and specificity of 94.3% and 62.5%, and positive and negative predictive value of 84.6% and 83.3% respectively. Positive CD8+ cell intracellular IFN-gamma plus Tc1/Tc2 < 50 could increase the positive predictive value to 92.3%. A multivariable model consisting of absolute neutrophil count (ANC), BM T cell intracellular IFN-gamma, Tc1/Tc2 ratio and HLA-DRB * 1501 phenotype of the patients was finally established.

CONCLUSIONThe multivariable model is superior to each of the single parameters in terms of predictive power of IST therapeutic outcome, and its higher accuracy and the clinical application make it potentially useful in practice.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; drug therapy ; immunology ; Child ; Feasibility Studies ; Female ; HLA-DR Antigens ; immunology ; Humans ; Immunosuppression ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Models, Statistical ; T-Lymphocyte Subsets ; immunology ; T-Lymphocytes ; immunology ; Treatment Outcome

Adolescent ; Fucosyltransferases ; genetics ; Gene Rearrangement ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Protein-Tyrosine Kinases ; genetics

OBJECTIVE: To investigate polymorphism distribution of the 5 Y-SNP loci in Jinan Han population, and evaluate their potential in forensic application. METHODS: Genotyping of 5 Y-SNP loci (M89, M9, M122, M134, M95) were executed in the sample of 103 unrelated Chinese male individuals in Jinan Han population by using fragment length discrepant allele specific PCR (FLDAS-PCR). RESULTS: In 5 Y-SNP loci, genetic polymorphism were identified in Jinan Han population, and the ranges of gene diversity(GD) were 0.093 3-0.491 2. Twenty different haplotypes were observed and the haplotypes diversity (HD) was 0.867 9. Six different haplogroups were detected according to international association of Y chromosome nomenclature. CONCLUSION Five Y-SNP loci and their haplogroups in Jinan Han population are highly polymorphic, which can provide more information for the genetic structure analysis and forensic genetics research in the region.
Alleles ; Asian People/genetics* ; China/ethnology* ; Chromosomes, Human, Y/genetics* ; Forensic Genetics/methods* ; Gene Frequency ; Genetic Markers ; Haplotypes ; Humans ; Male ; Polymerase Chain Reaction/methods* ; Polymorphism, Single Nucleotide/genetics*