![]() ![]() Using canine kidney cells as a model of renal tubules, we found that HGF-induced temporal up-regulation of Src activity and its scaffold protein, CDCP1, and that the ablation of CDCP1 robustly abrogated HGF-induced phenotypic changes, such as morphological changes and cell growth/proliferation. Here, we show that CUB domain-containing protein 1 (CDCP1) promotes HGF-induced compensatory renal growth. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis.Ĭompensatory growth of organs after loss of their mass and/or function is controlled by hepatocyte growth factor (HGF), but the underlying regulatory mechanisms remain elusive. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. FLT3‑TKD samples were associated with increased phosphorylation of activating tyrosines on the cytoplasmic Src-family tyrosine kinases FGR and HCK, and related signaling proteins. Finally, we detected nearly 30,000 phosphosites in these samples globally, AML samples were associated with the abnormal phosphorylation of specific residues in PTPN11, STAT3, AKT1 and PRKCD. We identified two cell surface proteins (CD180 and MRC1/CD206) expressed on AML blasts of many patients (but not healthy CD34+ stem/progenitor cells) that could represent novel targets for immunologic therapies, and confirmed these targets via flow cytometry. In samples with NPMc mutations, we identified several nuclear importins with post‑transcriptionally increased protein abundance, and showed that they interact with NPMc, but not wildtype NPM1. For example, samples with IDH1/2 mutations displayed elevated levels of the 2‑oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in mRNA levels for these genes we confirmed this finding in vitro. in all AML samples), and also, in patients with recurrent AML driver mutations. We identified examples of post-transcriptionally regulated proteins both globally (i.e. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. ![]() We have developed a deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls. Patient source (Asians or Caucasians) can be partially explained the different effects of FLT3-TKD in the prognosis of patients with AML. To be specific, FLT3-TKD represented a beneficial prognosis of DFS (HR = 0.56, 95% CI: 0.37–0.85) and OS (HR = 0.63, 95% CI: 0.42–0.95) for Asians, whereas it represented an adverse prognosis of DFS for Caucasians with AML (HR = 1.34, 95% CI: 1.07–1.67).įLT3-TKD revealed no significant effects on DFS and OS of patients with AML, which is consistent with the controversial status nowadays. However, meta-regressions demonstrated that patient source contributed to the high heterogeneity observed in the prognosis of FLT3-TKD in AML. We found that FLT3-TKD revealed no significant effect on disease-free survival (DFS) (HR = 1.12, 95% CI: 0.90–1.41) and overall survival (OS) (HR = 0.98, 95% CI: 0.76–1.27) in general. Twenty prospective cohort studies (n = 10,970) on the prognostic effect of FLT3-TKD in AML were included: 9,744 subjects with FLT3-WT and 1,226 subjects with FLT3-TKD. The sensitivity analysis was performed to evaluate the stability of findings in meta-analysis. Begg’s and Egger’s tests were performed to detect potential publication bias. Meta-regression model and subgroup analysis were used for heterogeneity analysis. Hazard ratio (HR) and its 95% confidence intervals (95% CIs) were used to determine the effect size. Hence, we performed a meta-analysis to investigate the prognostic significance of FLT3-TKD in patients with AML.Ī systematic retrieval of studies on FLT3-TKD in patients with AML was performed in PubMed, Embase, and Chinese National Knowledge Infrastructure databases on 30 September 2020. FLT3-ITD has been determined as an independent poor prognostic factor, but the prognostic impact of potentially metabolically related FLT3-TKD remains controversial. Internal tandem duplication (ITD) in the juxtamembrane domain and point mutations within the tyrosine kinase domain (TKD) are two distinct types of FLT3 mutations. Fms-like tyrosine kinase 3 (FLT3) gene mutations occur in approximately 30% of all patients with acute myeloid leukemia (AML). ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |