87Chantana POLPRASERT88Kamonlak LEECHAROENKIATMolecular study of large granular lymphocyte leukemia patients in Thai population (Project 2015)Characterization of the long non-coding RNA transcripts from chromosome 6q23 HBS1L-MYB intergenic region associated with fetal hemoglobin level (Project 2015)64and normal. CKD 2 and 4 weeks groups were induced by a chronic ischemic reperfusion (I/R) in a mouse model. In the effect of 2 and 4 weeks CKD on intestinal transporters, the intestinal mdr1a mRNA level was reduced by 48.80 and 73.00%, at 2 and 4 weeks after CKD induction, respectively. Additionally, cyp3a11 gene expression of 4 weeks CKD group was reduced by 66.68 %. Midazolam hydroxylation assay illustrated that intestinal CYP3A activity of 4 weeks CKD group was reduced by 19.40%. In conclusion, CKD is associated with a decrease in intestinal efflux drug transporters and CYP3A expression and activity. These reductions could explain the increased bioavailability of drugs used in CKD.Introduction: Large granular lymphocyte (LGL) leukemia belongs to chronic mature lymphoproliferative dis-orders of the T/natural killer (NK) lineage. This entity has 3 different subtypes which manifest differently. Diagnosis can be difficult and easily missed due to lack of specific diagnostic test. Methodology: We plan to establish diagnostic scheme for LGL leukemia by flow cytometry and PCR for STAT3 mutation. Flow cytom-etry was performed by six-color flow cytometry and STAT3 exon 20-23 was sequenced. Whole exome se-quencing was done in 2 cases of NK-LGL. Results: We collected 9 cases of LGL leukemia, 7 cases were T-LGL, 2 cases were NK-lymphocytosis and 2 cases were NK-LGL (aggressive NK leukemia). Both T-LGL and NK-lymphocytosis were indolent, 2 patients present with asymptomatic cytopenia. Only 1 case of T-LGL as-sociated with autoimmune disorder. Flow cytometry detected specific immunophenotype in all cases of LGL leukemia according to the criteria. Germline variant of STAT3 (c.1854C>T) was detected in 2 cases of T-LGL. In aggressive NK-LGL, we identified somatic mutation of TET2 by whole exome sequencing but STAT3 muta-tion was not detected. Conclusion: Large granular lymphocyte (LGL) leukemia is a rare entity in Thailand. Flow cytometry can be a diagnostic tool interpreted by expert. STAT3 mutation is not prevalent in Thai LGL leukemia patient might not be a molecular marker for LGL leukemia. However, absence of STAT3 mutation in this cohort might be due to small number of the patient or low sensitivity of technique.β-thalassemia/HbE is a blood disorder caused by impairment of β-globin production. Genome wide association study (GWAS) has identified the chromosome 6q23 HBS1L-MYB intergenic region (HMIR) as genetic modifier of fetal hemoglobin level in this disease; however, its significant is not elucidated. This study aims to detect and characterize the HMIR transcript in β-thalassemia/HbE erythroblasts. The presence of HMIR transcript in cultured erythroblasts was carried out by quantitative reverse transcription-polymerase chain reaction. The erythroblasts derived from β-thalassemia/HbE patients display increased expression of γ-globin mRNA and high HbF levels. All HMIR transcripts demonstrated greater than 4-fold down-regulation in β-thalassemia/HbE erythroblasts expressing high g-globin mRNA and HbF level. In order to characterize these HMIR transcripts, the 5ʹ and 3ʹ rapid amplification of cDNA ends (RACE) were carried out to detect the full length of the transcripts. Results of RACE products show size of the 5ʹend of each transcripts are more than 200 base pairs. These findings suggest that HMIR transcriptional activity is associated with HbF production in human erythroblasts that influence the beta-thalassemia phenotype for the novel therapy.
元のページ ../index.html#68