Despite continuous improvements of AML therapy, the prognosis of AML patients remains unsatisfactory. Recently, lncRNAs have been reported to participate in the development of AML. Our data demonstrated that MMP15 and LINC00963 were upregulated and miR-608 was decreased in AML cells (THP-1, HL-60, HEL and MOLM-13) compared to HS-5 cells. RT-qPCR results showed that LINC00963 levels were higher in the serum and bone marrow of AML cases than in controls. Moreover, overexpression of LINC00963 promoted AML cell growth and EMT progression in both THP-1 and HL-60 cells. Furthermore, miR-608 levels were downregulated in the serum and bone marrow of AML cases compared with controls, and Pearson's correlation analysis indicated that LINC00963 was negatively correlated with miR-608 in the serum and bone marrow of AML samples. In addition, we demonstrated that LINC00963 sponged miR-608 expression and that MMP-15 was a target of miR-608 in AML cells. Finally, rescue experiments indicated that ectopic expression of LINC00963 accelerated cell growth and EMT development by modulating MMP-15. These data demonstrated that LINC00963 acted as an oncogene and may be a potential target for AML treatment.
Deletion 7q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(7q) in patients following cytotoxic therapies is highly suggestive of an emerging therapy-related myeloid neoplasm. In this study, we describe 39 patients who acquired del(7q) as a sole abnormality in their bone marrow following cytotoxic therapies for malignant neoplasms. The median interval from cytotoxic therapies to detection of del(7q) was 40 months (range, 4-190 months). Twenty-eight patients showed an interstitial and 11 showed a terminal 7q deletion. Fifteen patients (38%) had del(7q) as a large clone and 24 (62%) as a small clone. With a median follow-up of 21 months (range, 1-135 months), 18 (46%) patients developed therapy-related myeloid neoplasms, including all 15 patients with a large del(7q) clone and 3/24 (12.5%) with a small clone. Of the remaining 21 patients with a small del(7q) clone, 16 showed no evidence of therapy-related myeloid neoplasms and 5 had an inconclusive pathological diagnosis. We conclude that isolated del(7q) emerging in patients after cytotoxic therapy may not always be associated with therapy-related myeloid neoplasms in about half of patients. The clone size of del(7q) is critical; a large clone is almost always associated with therapy-related myeloid neoplasms, whereas a small clone can be a clinically indolent or transient finding.
Abstract: The role of the programmed death-1 (PD-1) signaling pathway in tumor immunotherapy is becoming increasingly important, and several PD-1-blocking agents have been approved by the US Food and Drug Administration. PD-1-blocking therapy alone or in combination with other therapeutic modalities has become a standard treatment for several kinds of solid tumors. However, sarcomas are not indications for anti-PD-1 therapy. Sarcomas are a group of heterogeneous diseases that can currently only be cured by surgery at the early stage. No effective treatments exist for sarcoma patients in advanced stages. Owning to the diversity of sarcomas, it is very difficult to conduct randomized controlled clinical studies on specific subtypes of sarcomas. Although clinical studies of sarcomas continue, few breakthroughs in the treatment of sarcomas have been achieved over the past decades. This review summarizes recent progress in anti-PD-1 therapy for sarcomas. Based on the published data, PD-1 blockade may be more effective in combination with other modalities for the treatment of sarcomas. In addition, biomarkers may be used to ascertain sensitivity to PD-1 blockade in sarcoma patients. Keywords: PD-1 blockade, immunotherapy, sarcoma
Abstract Background To study the lncRNA-mRNA interaction network structure and analyze the possible target mRNAs among the differentially expressed lncRNAs between healthy adults, newly diagnosed multiple myeloma patients, and refractory relapsed multiple myeloma patients. Methods Public sequence data files were downloaded from the Sequence Read Archive (SRA). Totally 23 RNA-seq samples (GSE110486) related to myeloma published in 2018 (including transcriptome data of bone marrow plasma cells from healthy adults, newly diagnosed multiple myeloma patients and recurrent patients) were acquired, further analyses of differential lncRNAs, lncRNAs-mRNA co-expression, and WGCNA expression module and cis regulatory gene were performed. In addition, we performed differential expression analysis of lncRNAs and enrichment analysis of target mRNA regulated by lncRNAs from multiple myeloma patients and healthy controls which in order to verify the functions of these lncRNAs and their target mRNAs. Results From the transcriptional samples in this study,1006 new lncRNAs were identified, which including 707 lncRNAs specifically up-regulated and 283 specifically down-regulated in relapsed myeloma. The mRNA genes co-expressed with specific lncRNAs in relapsed multiple myeloma were mainly enriched in the extracellular matrix organization, platelet activation, cell adhesion, inflammation response, T cell co-stimulation and immune response pathways. Target mRNA regulated by DE lncRNAs including IL23R, ELF3, IL32, TMIGD2, CD28, CD5, TNF, CX3CR1, ADAMTS20 etc, by GO analysis, these target genes were enriched into many biological processes, such as innate immunity, apoptosis and positive regulation of apoptosis. The cis-regulated lncRNA of these target mRNAs include U62631.5, XLOC_062939 and XLOC_027240, and their cis-regulatory targets include CD22, SSX1 and DCC. lncRNAs and enrichment analysis of target mRNA regulated by lncRNAs from multiple myeloma patients and healthy controls was consistent with the previous analysis. Conclusion Target mRNAs regulated by DE lncRNAs and their cis-regulatory targets are involved in the immune cells remodeling of gene expression patterns during multiple myeloma relapse, and may have an important function in this pathological process, it deserves further study as a potential target for the treatment of multiple myeloma.
In order to investigate the influence of iron deficiency on the mRNA expression of iron regulatory protein (IRP(2)) mRNA and ferritins (FN) in intestinal mucosa of rat, the animal model of rat with nutritional iron deficiency was established. According to the measurement of serum iron (sI), serum fertitin (sFn) and Hb, the experiments were divided into 4 groups: control group, recessive iron deficiency group, mild iron deficiency group and moderate iron deficiency group. sI was measured by flame assay and sFN was measured by radioimmunoassay, the expressions of irp(2) mRNA and fn mRNA were detected by RT-PCR. The results showed that (1) with aggravation of iron deficiency, the levels of sI and sFN in experimental groups decreased and had significant difference from that in control group, except sI level in the recessive iron deficiency group; (2) with aggravation of iron deficiency, the expression of irp(2) mRNA in duodenum mucosa elevated, and the expressions of irp(2) mRNA in moderate iron deficiency group and mild iron deficiency group were higher than that in control group (p < 0.01), the expression of irp(2) mRNA in moderate iron deficiency group was higher than that in recessive iron deficiency group (p < 0.05), but the expression of irp(2) mRNA did not showed statistical difference between mild iron deficiency group and moderate iron deficiency group (p > 0.05); (3) with aggragation of iron deficiency, the expression of fn mRNA in dudemum mucosa decreased, the expression levels fn mRNA in control and moderate groups were highest and lowest, respectively, there were significant differences between experimental and control groups (p < 0.05), and between experimental groups (p < 0.05); (4) the expression of irp(2) mRNA and fn mRNA in moderate iron difficiency group showed negative correlation (r = 0.662, p < 0.05). It is concluded that IRP(2) protein serves as an important regulator of iron metabolism in the human body, and regulates iron uptake from the intestine by controlling the expression of fn mRNA at the post transcriptional level.
Purpose: This study screened serum proteins to identify potential biomarkers for childhood B-cell and T-cell acute lymphoblastic leukemia (ALL). Patients and methods: Serum collected from 20 newly diagnosed B-cell ALL, 20 T-cell ALL and 20 healthy children. The peptides from these samples were subjected to iTRAQ. Differentially expressed proteins (DEPs) were further validated by ELISA in 24 B-ALL, 24 T-ALL, and 24 healthy children. Results: Bioinformatics analysis revealed several pathways, including atherosclerosis signaling, interleukin signaling and production in macrophages and clathrin-mediated endocytosis signaling, that were closely related to childhood T-cell ALL. Furthermore, four selected proteins, namely LRG1, S100A8, SPARC and sL-selectin, were verified by ELISA. These results were consistent with the results of the proteomics analysis. Conclusion: Serum S100A8 may serve as new diagnostic biomarkers in childhood B-cell ALL and T-cell ALL. Keywords: B-cell ALL, T-cell ALL, proteomics, acute lymphoblastic leukemia, children, serum, isobaric tags for relative and absolute quantitation, ingenuity pathways analysis
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