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Introduction The aim of the study was to determine molecular genetic and clinical characterization of acute myeloid leukemia (AML) with trisomy 8 as the sole chromosome abnormality, a recurrent but rare chromosomal abnormality in AML.Methods Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for gene rearrangement and next-generation sequencing (NGS) were performed on sole trisomy 8 AML patients.Results A total of 35 AML patients with trisomy 8 as the sole chromosome abnormality were screened. The most frequently mutated genes were DNMT3A(37.1%), RUNX1(28.6%), FLT3-ITD(28.6%), IDH2(22.9%), NPM1(17.1%), and ASXL1 (14.3%). The sole +8 AML patients exhibited more mutations in RUNX1 (28.6% vs. 4.8%, P = 0.001) and ASXL1 (14.3% vs. 4.8%, P = 0.039) by comparing with normal karyotype AML (NK AML) patients(n = 63). The sole +8 AML patients(n = 35) with RUNX1 or IDH2 mutations showed significantly lower WBC counts, while FLT3-ITD showed higher white blood cell (WBC) counts as compared to the corresponding wild-type groups. Total of 45.7% patients achieved complete remission (CR) after the first induction therapy. The CR rate of patients with FLT3-ITD or IDH1 mutation was significantly lower than that in the corresponding wild-type cases (P = 0.047, 0.005, respectively). The median overall survival (OS) and disease-free survival (PFS) were 18.0 (95% CI: 10.8–25.2) and 10 (95% CI: 6.7–13.3) months, respectively. FLT3-ITD mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were independent prognostic markers for OS in multivariable analysis.Conclusion The results suggest a possible association between trisomy 8 and additional mutations that may influence clinical feature and prognosis.

Introduction Several studies have confirmed that mutations in the Wilms tumor 1 (WT1) gene occur in adult acute myeloid leukemia (AML). However, few data are available regarding the incidence of WT1 mutations in CEBPAmut AML and their impact.Methods We retrospectively analyzed the frequency and clinical impact of WT1 mutations in 220 newly diagnosed AML patients with CEBPA mutations(CEBPAmut). Chromosome karyotype analysis was performed by R or G banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT–PCR). Mutations were detected with a panel of 112mutational genes using next-generation sequencing (NGS).Results Overall, 30 WT1 mutations were detected in 29 of the 220 CEBPAmut AML patients (13.18%) screened. These mutations clustered overwhelmingly in exon 7 (n=16). WT1 mutations were found to be significantly more frequent in AML patients with double-mutated CEBPA (CEBPAdm) than in AML patients with single-mutated CEBPA (17.36%vs. 8.08%, P = 0.043). Among WT1-mutated patients, the most common co-mutation was FLT3-ITD (n = 7, 24.14%), followed by NRAS (n = 5, 17.24%), CSF3R (n = 4, 13.79%), GATA2 (n = 4, 13.79%), and KIT (n = 4, 13.79%). The most frequent functional pathway was signaling pathways inas many as 62.07% of cases. Notably,the concomitant mutations in epigenetic regulatorswere inversely correlated with WT1 mutations(P = 0.003). CEBPAdm AML patients with WT1 mutations had inferior relapse-free survival, event-free survival and overall survival compared with patients CEBPAdm AML without WT1 mutations (P = 0.002, 0.004, and 0.010, respectively).Conclusion Our data showed that WT1 mutations are frequently identified in CEBPAmut AML, especially in CEBPAdm AML. CEBPAmut AML patients with WT1 mutations show distinct spectrum of comutations. In the context of CEBPAdm AML, WT1 mutations predict a poor prognosis.

The natural history of primary hypereosinophilia remains poorly defined, given the underlying disease heterogeneity. Recently, targeted NGS helps to establish clonality in a subset of patients with hypereosinophilia. We first reported the clonal evolution in a long-term follow-up patient with hypereosinophilia. This case initially presented with chronic eosinophilic leukemia, not otherwise specified (CEL-NOS), successively transformed to myelodysplastic syndromes (MDS) and acute myeloid leukemia(s-AML). We identified three mutations at CEL-NOS phase, five and seven mutations at MDS and s-AML stages, respectively. Our data illustrate the clonal dynamic process associated with disease evolution from CEL-NOS to s-AML. Keywords: Hypereosinophilia, Clonal evolution, Next generation sequencing

Ultrafine-grain size of ~1µm was achieved in an AZ31B Mg alloy wires with high strength prepared by cold drawing and subsequent annealing in the present study. Effects of cold-drawn area reduction (CAR) on strain hardening, recrystallized grain refinement and annealing temperature were investigated. The results showed that the maximum cold area reduction as high as 65.1% could be reached at room temperature, which resulted in the notable strain hardening, grain refinement and the decrease of annealing temperature. [ABSTRACT FROM AUTHOR]

AZ31 magnesium alloy sheets with a thickness of about 2mm were prepared by using a unique hot rolling process which was featured by heating the rolls during rolling. Two different rolling routes were used to achieve the final thickness through 6 passes of rolling. The major rolling parameters were chosen as the same for both rolling routes except that the roll temperature was set to be 400°C for route A and the 1st to 4th passes of route B, but lowered to 350°C for the 5th and 6th passes of route B. The microstructure and mechanical properties of the alloy sheets were comparatively investigated. The results showed that dynamic recrystallization occurred during hot rolling, and by choosing the processing parameters appropriately the grain size could be refined steadily with increasing rolling passes. The final alloy sheet prepared by 6 passes of rolling via the rolling route B was featured by a very fine microstructure, with the grain size being 5μm in average. Correspondingly, it presented very high strength and tensile elongation, with its yield strength and tensile elongation achieving 206MPa and 26.4% in the transverse, and 196MPa and 27.6% in the rolling direction, respectively. [ABSTRACT FROM AUTHOR]