Mutations of FBXW7 in Adult T-Cell Acute Lymphocytic Leukemia / 中国实验血液学杂志

<p><b>BACKGROUD</b>F-Box and WD40 domain containing protein 7 gene (FBXW7) is part of the E3 ubiquitin ligase complex that controls the turnover of various proteins including NOTCH1, c-MYC and Cyclin E.</p><p><b>OBJECTIVE</b>To investigate the mutations of FBXW7 gene in adult T-cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>Exon 5-12 of FBXW7 were amplified, cloned and sequenced in 54 adult T-ALL patients; the frequency, position and types of FBXW7 mutation were analyzed; the co-existing of mutations with NOTCH1 and their relevant prognostic significance were explored as well.</p><p><b>RESULTS</b>FBXW7 mutations were identified in 11.1% of adult T-ALL patients. A total of 4 types of point mutations (R465H, R465L, R479P and R505C) and 1 deletion/insertion mutation were observed, and all of them located in WD40 domain of FBXW7. In addition, co-existing mutations with NOTCH1 were identified in 83.3% of patients with FBXW7 mutation. Notably, the co-existed NOTCH1 mutations, including 3 point mutations (L1574P, L1596H and L1600P) and 2 deletion/insertion mutations located in HD domain. Furthermore, patients with FBXW7 mutation only had significantly longer overall survival compared with those without mutation (P=0.049).</p><p><b>CONCLUSION</b>FBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.</p>

Mutation and expression of PAX5 gene in adult acute lymphoblastic leukemia / 中国实验血液学杂志

PAX5 is an important transcription factor of paired-box(PAX) family. The aim of this study was to investigate the mutations and expression of PAX5 and its clinical significance in adult patients with acute lymphoblastic leukemia (ALL). Reverse transcription polymerase chain reaction (RT-PCR) and genomic PCR were performed to detect the deletions of PAX5 and point mutations of PAX5 exon 2-10 in 101 cases of adult ALL and were confirmed by cloning and sequencing. In addition, quantitative PCR (qPCR) was performed to evaluate the expression of PAX5. Furthermore, the correlations of mutations and expression of PAX5 with clinical parameters were analyzed, and the prognostic significance was evaluated as well. The results showed that PAX5 mutations were observed in 8 of 101 (7.9%) patients with B-ALL. A total of 9 types of mutations were detected, including 4 types of deletions, 4 types of point mutations and 1 insertion mutation; percentage of patients with age ≥ 50 years was higher in PAX5 mutation group than in wide-type group (62.5% vs 21.5%,P = 0.031) . The statistical differences were observed in B-cell subtype, initial platelet count and immunophenotypes between high and low expression of PAX5 (P < 0.05) . In addition, patients with high expression of PAX5 had higher first complete remission rate (86.7% vs 62.5%, P = 0.030) and 6-month overall survival rate (75.0% vs 50.0%, P = 0.034) compared with patients with low expression of PAX5. It is concluded that deletion/insertion/point mutations and aberrant expression of PAX5 can be observed in adult patients with B-ALL. Mutations and aberrant expression of PAX5 correlated with clinical parameters and have important clinical significance.

Mutation and expression of LEF1 in adult acute lymphocytic leukemia and their clinical significance / 中国实验血液学杂志

Lymphoid enhancer factor 1 (LEF1) is a key transcription factor in Wingless-type (Wnt) pathway. The present study was aimed to explore the genetic mutation and expression of LEF1, and their clinical significance in adult patients with acute lymphocytic leukemia (ALL). Genomic DNA was amplified and sequenced to detect the mutation of LEF1 in 131 newly diagnosed adult patients with ALL. Quantitative PCR (qPCR) was performed to detect the expression of LEF1. Moreover, the correlations between mutations and expression of LEF1 with clinical characteristics were analyzed. The results showed that the frequency of LEF1 mutation in adult ALL was 3.1% (4/131) and all of them were point mutations located in exon 2 and 3; the median white blood cell count and median percentage of blasts at diagnosis were significantly higher in LEF1 high expression group than in low expression group (70.6 × 10⁹/L vs 26.2 × 10⁹/L)(P = 0.010); (81.0% vs 57.0%) (P = 0.014); in addition, the percentage of patients with Philadelphia chromosome positive and patients in high-risk group significantly increased in LEF1 high expression group compared with that in low expression group (66.7% vs 36.5%) (P = 0.038); (79.2% vs 56.2%) (P = 0.044). It is concluded that high expression of LEF1 may play an important role on development of adult ALL.

Observation of clinical efficacy of acupuncture for cerebral vasospasm after embolization of ruptured aneurysms / 中国针灸

<p><b>OBJECTIVE</b>To observe the improvement of acupuncture in cerebral vasospasm (CVS) after embolization of ruptured aneurysms.</p><p><b>METHODS</b>Sixty cases were randomly divided into two groups, an acupuncture-medication group and a conventional treatment group, 30 cases in each one. The cases of CVS in conventional treatment group were treated with Nimodipine. In acupuncture-medication group, on the basis of the treatment as conventional treatment group, Baihui (GV 20) and Fengchi (GB 20) were selected as the main acupoints in the treatment of CVS. The treatment lasted for 3 weeks. Hunt-Hess scale for the standard assessment was adopted to determine the severity of disease before and after treatment and compare the efficacy between two groups. The transcranial Doppler (TCD) was conducted on the 1st, 4th, 7th, 10th, 14th and 21st days successively after operation, and the average flow velocity of 3 pairs of vessels (ACA, MCA, and PCA) was recorded. CT perfusion (CTP) was taken to test cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) on the 1st, 7th, 14th and 21st days successively.</p><p><b>RESULTS</b>The improvement of Hunt-Hess scale in acupuncture-medication group was superior to that in conventional treatment group (P < 0.05). The analysis of variance (ANOVA) was adopted in the comparison of ACA, MCA, PCA, CBF, CBV and MTT between two groups. The results showed that the therapy in either group achieved the effect on CVS (all P < 0.05). But, the improvements in the above mentioned indices in acupuncture-medication group were superior to those in conventional treatment group (all P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture at Baihui (GV 20) and Fengchi (GB 20) down-regulates the peak values or upregulates the valley values. It releases the peak of CVS effectively, improves the clinical prognosis significantly and is the effective therapy for CVS after subarachnoid hemorrhage.</p>