RESULT: A total of 24 and 32 somatic variants were identified in presentation and relapse samples respectively with an average of 4.0 variants per patient at presentation and 5.3 variants per patient at relapse, with SNVs being more frequent than indels at both disease stages. All patients have somatic variants in at least one gene that is frequently mutated in AML at both disease presentation and relapse, with most of these variants are classic AML and recurrent hotspot mutations including NPM1 p.W288fs, FLT3-ITD, NRAS p.G12D and IDH2 p.R140Q. In addition, we found two distinct clonal evolution patterns of relapse: (1) a leukemic clone at disease presentation acquires additional mutations and evolves into the relapse clone after the chemotherapy; (2) a leukemic clone at disease presentation persists at relapse without the addition of novel somatic mutations.
CONCLUSIONS: The findings of this study suggest that the relapse-initiating clones may pre-exist prior to therapy, which harbor or acquire mutations that confer selective advantage during chemotherapy, resulting in clonal expansion and eventually leading to relapse.
OBJECTIVES: To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function.
DATA SOURCES AND METHODS: Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data.
RESULTS: MSC-treated group showed significantly lower risk of mortality than the control group (p = 0.03). No statistical significance was observed on the incidence of AEs (p = 0.78) and SAEs (p = 0.44), and the levels of CRP (p = 0.06) and IL-6 (p = 0.09).
CONCLUSION: MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation.
REGISTRATION: This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730).
METHODS: We used multiplex array technology to simultaneously detect and quantify 32 plasma analyte (22 reported analytes and 10 novel analytes) levels in 38 patients.
RESULTS: In our study, 16 analytes are found to be significantly deregulated (13 higher, 3 lower, Mann-Whitney U-test, P-value <0.005), where 5 of them have never been reported before in AML. We predicted a seven-analyte-containing multiplex panel for diagnosis of AML and, among them, MIF could be a possible therapeutic target. In addition, we observed that circulating analytes show five co-expression signatures.
CONCLUSIONS: Circulating analyte expression in AML significantly differs from normal, and follow distinct expression patterns.