The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

NeoPeptide: an immunoinformatic database of T-cell-defined neoantigens.

Therapeutic vaccines represent a promising immunotherapeutic modality against cancer. Discovery and validation of antigens is the key to develop effective anti-cancer vaccines. Neoantigens, arising from somatic mutations in individual cancers, are considered as ideal cancer vaccine targets because of their immunogenicity and lack of expression in normal tissues. However, only few databases support convenient access to these neoantigens for use in vaccines. To address this gap, we developed a web-accessible database, called NeoPeptide, which contains most of the important characteristics of neoantigens (such as mutation site, subunit sequence, major histocompatibility complex restriction) derived from published literature and other immunological resources. NeoPeptide also provides links to resources for further characterization of the novel features of these neoantigens. NeoPeptide will be regularly updated with newly identified and published neoantigens. Our work will help researchers in identifying neoantigens in different cancers and hasten the search for appropriate cancer vaccine candidates.

Comparison of infection eradication rate of using articulating spacers containing bio-inert materials versus all-cement articulating spacers in revision of infected TKA: a systematic review and meta-analysis.

PURPOSE: To assess the infection eradication rate when using two types of articulating spacers (prosthetic articulating spacers and all-cement articulating spacers) in two-stage revision of infected total knee arthroplasty (TKA). METHODS: We comprehensively searched PubMed, Embase, and the Cochrane Library databases and performed a systematic review and meta-analysis of retrospective comparative studies assessing two types of articulating spacers. A quality assessment of the included studies was performed following the STROBE statement. RESULTS: Thirty retrospective studies, including a total of 821 knees, were identified. The pooled infection control rates in stage I were as follows: 0.98 (95% confidence interval [CI], 0.97 to 1.00) and 0.98 (95% CI, 0.96 to 0.99) for the prosthetic articulating spacer group and all-cement articulating spacer group, respectively. The pooled postoperative reinfection rate was 0.05 (95% CI, 0.03 to 0.08) for the prosthetic spacer group and 0.03 (95% CI, 0.01 to 0.06) for the all-cement spacer group. Results of the subgroup analyses showed that the weight of the antibiotic cement, antibiotic type, mean period of spacers in situ, postoperative antibiotic treatment period, and postoperative antibiotic treatment approach had no effect on the reinfection rates (p < 0.05). CONCLUSIONS: Compared to all-cement articulating spacers, articulating spacers containing bio-inert materials have a similar infection control rate but a higher postoperative reinfection rate. Although the 95% CIs of reinfection rates in the two groups overlapped, our results indicate that articulating spacers containing bio-inert materials may be associated with higher reinfection rates and poorer clinical outcomes than all-cement articulating spacers.

Pulsed electromagnetic field induces Ca2+-dependent osteoblastogenesis in C3H10T1/2 mesenchymal cells through the Wnt-Ca2+/Wnt-ß-catenin signaling pathway.

Pulsed electromagnetic fields (PEMFs) are effective in healing fractures and improving osteoporosis. However, their effect on mesenchymal cells remains largely unknown. In this study, the effects of PEMF on osteoblastogenesis and its underlying molecular signaling mechanisms were systematically investigated in C3H10T1/2 cells. C3H10T1/2 mesenchymal cells were exposed to 30-Hz PEMF bursts at various intensities for 3 consecutive days. The optimal PEMF exposure (30 Hz, 1 mT, 2 h/day) was applied in subsequent experiments. Our results suggest that intracellular [Ca2+]i in C3H10T1/2 cells can be upregulated upon exposure to PEMF and that PEMF-induced C3H10T1/2 cell differentiation was Ca2+-dependent. The pro-osteogenic effect of PEMF on Ca2+-dependent osteoblast differentiation was then verified by alkaline phosphatase (ALP) and von Kossa staining. Furthermore, PEMF promoted the gene expression and protein synthesis of the Wnt/ß-catenin pathway. Increased [Ca2+]i in the nucleoplasm was followed by the mobilization and translocation of ß-catenin into the nucleus in C3H10T1/2 cells. A model of Wnt/ß-catenin signaling and the Wnt/Ca2+ signaling network is proposed. Taken together, these findings indicated for the first time that PEMF induces osteoblastogenesis through increased intracellular [Ca2+]i and the Wnt-Ca2+/Wnt-ß-catenin signaling pathway in C3H10T1/2 mesenchymal cells.