RESUMO
<p><b>OBJECTIVE</b>To analyze a hereditary hemorrhagic telangiectasia(HHT) family Activin receptor-like kinase 1(ACVRL1), Endoglin (ENG) and Mothers against decapentaplegic homolog 4 (MADH4, SMAD4) gene mutation, meanwhile, to observe the curative effect of thalidomide in treatment of HHT patients.</p><p><b>METHODS</b>The clinical feature of the HHT family was analyzed, the polymerase chain reaction (PCR) combined with Sanger sequencing of ACVRL1, ENG and SMAD4 were used to investigate the proband. The suspicious mutations were further detected in the other 7 family members. Proband was treated with thalidomide (100 mg/day) for 6 months, and the frequency and quantity of bleeding and blood transfusion frequency were assayed to evaluate the curative efficacy.</p><p><b>RESULTS</b>One ACVRL1 mutation (c.1231C>T) was identified in proband(II-1) and the other 4 family members(II-2, III-1, III-2, III-3), which was reported as a pathogenic gene and revealed cosegregation with HHT clinical phenotype. One ENG mutation (c.1096G>C) was previously reported as gene polymorphism, which was identified in some family members(II-1, II-3, III-1, III-2) without cosegregation with clinical phenotype. No gene mutation was found in SMAD4. After thalidomide treatment, the frequency and quantity of bleeding and blood transfusion frequncy in the proband were reduced, hemoglobin concentration and serum iron level were increased.</p><p><b>CONCLUSION</b>There is phenotypic heterogeneity in hereditary hemorrhagic telangiectasia and the features are age-dependent, the pathogenic gene of this pedigree is ACVRL1 mutation (c.1231C>T;p. R 411 W). Thalidomide is effective for the treatment of hemorrhage in hereditary hemorrhagic telangiectasia.</p>
RESUMO
<p><b>OBJECTIVE</b>To investigate the clinical characteristics of 31 acute myeloid leukemia (AML) patients with chromosome 21 aberrations.</p><p><b>METHODS</b>Karyotypes of 168 newly diagnosed AML patients in Second Xiangya Hospital from Jan 2014 to July 2016 were reviewed for the presence of chromosome 21 aberrations (accounting for 18.45%). Clinical manifestation, as well as prognostic gene mutations distribution and immune classification were analyzed.</p><p><b>RESULTS</b>Out of 168 AML newly diagnosed patients, 31 cases with chromosome 21 aberrations including t(8;21) accounting for 67.74% (21/31), and trisomy 21 (16.13%,5/31), 2 variants were found as t(1; 21) and t(1; 21; 8); 77 cases had normal karyotype, and 60 cases possessed other chromosomes aberrations. Statistically significant differences did not exist among age, sex and white blood cell count (P>0.05). However, the 21 cases in chromosome aberrations group were predisposed to lower hemoglobin and platelet count(P<0.05). 5 cases of Trisomy 21 were characterized by M5 2 cases, M1 one case, M2 one case M4 one case. And the rate of C-kit/D816V mutation was higher in t(8;21) aberrations group when 7 prognostic genes including FLT3/ITD, C-kit/D816V, NPM1, DNMT3A, TET2 were analyzed, and the immune classification of t(8; 21) aberration group inclined to CD19, CD34but CD33, CD64. And trisomy 21 displayed a trend to CD34and CD7.</p><p><b>CONCLUSION</b>Chromosome 21 is easily involved in acute myeloid leukemia. The patients with involvement of this aberration have characteristic clinic changes.</p>
RESUMO
<p><b>BACKGROUND</b>Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.</p><p><b>METHODS</b>HHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.</p><p><b>RESULTS</b>The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.</p><p><b>CONCLUSIONS</b>Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.</p>