Association of Next Generation Sequencing Based Genotypic Profiling with MICM Characteristics in NPM1 Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) by analyzing the association between next-generation sequencing (NGS) profiles and MICM characteristics in patients with this AML subtype.@*METHODS@#Data of 238 NPM1mut patients with available NGS information on 112 genes related to blood disease was collected, and χ2 test and nonparametric test were used to analyze the distribution association between NGS-detecting mutations and conventional MICM parameters.@*RESULTS@#In entire NPM1mut cohort, totaling 240 NPM1 mutation events were identified, of whom 10 (10/240, 4.2%) were missense mutations, which did not involve any W288 or W290 locus and were found exclusively in NPM1mut/FLT3-ITD- group. All but one of these missense mutations (9/10, 90%) were accompanied by AML subtype-defining recurrent cytogenetic or molecular abnormalities, of which 7 cases were in the low risk and 2 in the high risk. NPM1mut occurred solely as an insertion/deletion (indel) type in the NPM1mut/FLT3-ITD+ group. The incidence of favorable plus unfavorable karyotypes in NPM1mut/FLT3-ITD- group was higher than in NPM1mut/FLT3-ITD+ group (6.4% vs. 0, P=0.031). The positive rates of CD34 and CD7 in NPM1mut/FLT3-ITD+ group were significantly higher than in NPM1mut/FLT3-ITD- group (CD34: 47.9% vs. 20.6%, P<0.001; CD7: 61.5% vs. 29.9%, P<0.001). Logistic analysis showed that FLT3-ITD independently predicted for CD34+ and CD7+ [odds ratio (OR)=5.29, 95%CI: 2.64-10.60, P<0.001; OR=3.47, 95%CI: 1.79-6.73, P<0.001; respectively]. Ras-pathway mutations independently predicted for HLA-DR+ (OR=4.05, 95%CI: 1.70-9.63, P=0.002), and KRAS mutation for MPO- (OR=0.18, 95%CI: 0.05-0.62, P=0.007). TET2/IDH1 mutations independently predicted for CD34- and CD7- (OR=0.26, 95%CI: 0.11-0.62, P=0.002; OR=0.30, 95%CI: 0.14-0.62, P=0.001; respectively), and MPO+ (OR=3.52, 95%CI: 1.48-8.38, P=0.004). DNMT3A-R882 independently predicted for CD7+ and HLA-DR+ (OR=3.59, 95%CI: 1.80-7.16, P<0.001; OR=13.41, 95%CI: 4.56-39.45, P<0.001; respectively), and DNMT3A mutation for MPO-(OR=0.35, 95%CI: 1.48-8.38, P=0.004).@*CONCLUSION@#Co-existing FLT3-ITD in NPM1mut AML independently predicts for CD34+ and CD7+, co-existing Ras-pathway mutation for HLA-DR+ and MPO-, co-existing TET2/IDH1 mutation for CD34-, CD7-, and MPO+, and co-existing DNMT3A mutation for HLA-DR+, CD7+, and MPO-, thereby providing a new mechanism explanation for the immunophenotypic heterogeneity of these AML patients.

The Mutated Gene Sequenced by NGS and the Correlation of Their Coexistent Mutual Exclusiveness in NPM1 Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1@*METHODS@#The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1@*RESULTS@#Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1@*CONCLUSION@#Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1

Research Related to Neural Protection of Hypoxic and Hyperoxic Preconditioning after Spinal Cord Injury (review) / 中国康复理论与实践

Repeated acute intermittent hypoxia promotes the expression of growth factors and neurotrophic factors, as well as the key molecules for neural protection and plasticity. Hypoxic preconditioning may improve the survival rate of transplant-ed stem cells and protect the neural function. Meanwhile, acute intermittent hypoxia can be an approach to improve re-spiratory function after spinal cord injury. Hyperbaric oxygen may improve the neural tolerance to hypoxia and isch-emia, to protect the structure of cells and tissues, and promote the neuranagenesis. It is important to study the role of hy-poxic and hyperoxic preconditioning in spinal cord injury.

Systematic reviews of ganciclovir combined with traditional Chinese medicine for herpes simplex keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the efficacy and safety of ganciclovir combined with traditional Chinese medicine ( TCM ) in treatment of herpes simplex keratitis (HSK). ·METHODS: All randomized controlled trials ( RCTs) of ganciclovir combined with TCM for HSK were searched in CNKI, VIP, Wanfang, PubMed, Cochrane Library and EMbase database. The clinical endpoints of the total effective rate, relapse rate, heal time, and adverse reaction rate were collected to assess the drugs' efficacy and safety. The improved Jadad Scale was used to evaluate the methodological quality of included literatures. The RevMan5. 3 software and Stata 12. 0 were applied for meta-analysis. ·RESULTS: We finally included 15 RCTs involving 1 285 patients. As for the total effective rate, relapse rate and heal time, significant differences were noted between ganciclovir combined with TCM group and ganciclovir alone group. For the total effective rate, RR and 95% CI were 1. 23 ( 1. 15 ~ 1. 31 ) according to the number of patients and 1. 18(1. 02-1. 38) according to the number of diseased eyes. For relapse rate, RR and 95% CI were 0. 25 (0. 17-0. 36). For heal time, MD and 95% CI were -7. 58 (-10. 89 to - 4. 26 ). No statistic difference of adverse reaction rate between the two groups was observed [RR=0.53, 95% CI(0. 23-1. 22)]. The side effects in the two groups were mild and could be relieved by themselves. ·CONCLUSION: The ganciclovir combined with TCM can improve the total efficacy, reduce the relapse rate, and shorten the course of treatment for HSK with good safety.

Detection of ASXL1 Mutation and CALR Mutation Coexistance in Patients with Ph Negative Myeloproliferative Neoplasm and Its Clinical Gignificance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the coexistence of ASXL1 and CALR gene mutations in patients with essential thrombocytheima (ET) and with primary myelofibrosis(PMF), and to compare the differences of clinical characteristics between ET and PMF patients carrying ASXL1 and CALR mutations, and ET and PMF patients carrying solitary gene mutation, and ET and PMF patients without any mutations.</p><p><b>METHODS</b>The mutations of ASXL1 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 263 essential ET patients and 29 PMF patients were detected by PCR amplification followed by direct sequencing of genomic DNA. The JAK2V617F mutations were used by allele specific PCR detection.</p><p><b>RESULTS</b>72.6%(212/292)of patients harbored at least one mutation. The incidences of ASXL1 and CALR mutations were 5.8% and 30.5%, respectively. The frequencies of JAK2V617F and MPL mutations were 39.0% and 2.4%, respectively. 5.1%(15/292) of patients had double mutations, including ASXL1 and CALR(n=11), ASXL1 and JAK2V617F(n=2), MPL and CALR(n=1) and ASXL1 and MPL(n=1). The frequency of concurrent ASXL1 and CALR mutations was found to be high. Significant difference was found on hemoglobin levels and platelet counts between CALR and ASXL1 mutations and single mutation (P<0.05),however, the difference on leukocyte counts and median age was not found. Compared with negative patients, the presence of ASXL1 and CALR mutations was found to be significantly correlative with lower hemoglobin level (P=0.045), lower leukocyte count (P=0.002) and with higher platelet counts(P=0.001), but the difference of median age was not found.</p><p><b>CONCLUSION</b>The frequency of concurrent ASXL1 and CALR mutations is higher in ET patients. The coexistence of ASXL1 and CALR gene mutations significantly associated with lower hemoglobin level and higher platelet count.</p>

Mutation of CALR Gene in Patients with Chronic Myeloproliferative Neoplasm and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm(MPN) and to explore the clinical significance of CALR mutation.</p><p><b>METHODS</b>The peripheral blood of patients was collected and the genomic DNA was exacted, the 9 exon of CALR gene and the fragment of human thrombopoetic receptor(MPL) gene were amplified by PCR, the mutation of CALR and MPL genes was detected by using the direct sequencing, the JAK2 V617F mutation was detected by using allele spicific PCR.</p><p><b>RESULTS</b>The CALR mutations were detected in 13 patients out of 55 MPN patients (23.6%). The frequency of CALR mutation was 22.7% (10/44) in 44 essential thrombocythemia(ET) patients. A total of 3 types of CALR mutation were identified (type I c.1092_1143del52bp, n=5; type II c.1154_1155insTTGTC, n=4; type III c.1094_1139del46bp, n=1). CALR mutations occurred at a frequency of 27.2% in primary myelofibrosis (PMF), including type I (n=2) and type II (n=1). The incidence of JAK2 V617F was 58.1%(32/55), that in ET and PMF was 59.1%(26/44) and 54.5% (6/11), respectively. The mutations of MPL W515 were not detectable in all cases, and the simultaneous mutation of CARL and MPL W515 was not detected. The median age of patients with CALR mutation was significantly younger than that of patients with JAK2 mutations (48 vs 64 years of old, P<0.05). The levels of hemoglobin and leukocytes in patients with CARL mutations were significantly lower (P<0.05) but the level of plateletes was higher than that in patients with JAK2 V617F mutations (P<0.05). Deep venous thrombosis occurred in 4 of 35 ET patients with the JAK2 V617F mutation (n=4), but did not occurr in the patients with CALR mutation. Karyotype abnormality was detected in only one case among 48 patients by chromosome karyotype analysis.</p><p><b>CONCLUSION</b>The incidence of CALR mutation is high in ET and PMF patients without JAK2 V617F and MPL W515K mutations, which is associated with younger median age, lower leucocyte and hemoglobin levels, higher platelet counts, and rare thrombocytosis, compared with the patients with JAK2 V617F mutation.</p>