RESUMO
HLA-B*35:568 differs from HLA-B*35:03:01:01 by one nucleotide in exon 4.
Assuntos
População do Leste Asiático , Antígenos HLA-B , Humanos , Alelos , Análise de Sequência de DNA , Antígenos HLA-B/genética , NucleotídeosRESUMO
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis. The microarray revealed that 1011 lncRNAs and 2656 mRNAs differed in AML patients and 6069 lncRNAs and 5338 mRNAs differed in ALL patients from those in healthy controls. The GO terms and KEGG pathway annotation data revealed that the olfactory receptor activity, G-protein coupled receptor activity and olfactory transduction-related genes were significantly associated with AML and ALL. Co-expression network analysis indicated that 108 lncRNAs and 85 mRNAs were included in the co-expression network. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in AML and ALL using microarray technology and could provide basic information for new biomarkers or treatment targets to alleviate AML and ALL.
Assuntos
Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/metabolismo , Doença Aguda , Adulto , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA não Traduzido/genética , Transdução de Sinais/genéticaRESUMO
Sphingosine-1-phosphate receptor 1 (S1PR1), the G protein-coupled receptor 1 of sphingosine 1-phosphate (S1P), is crucial in the progression of various types of solid tumor through the positive regulation of antiapoptotic/prosurvival responses by S1PS1PR1 signaling. However, the role of S1PR1 in the progression of human acute myeloid leukemia (AML) remains to be fully elucidated. In the present study, the correlation between the expression level of S1PR1 and the growth and apoptosis of human AML cells was investigated. Using overexpression and RNA interference knockdown assays, it was shown that the expression of S1PR1 in several human myeloid leukemia cell lines contributed to the suppression of cell apoptosis and promotion of cell proliferation. S1PR1 inhibited the expression level of B cell lymphoma2associated X protein, a mitochondrionassociated apoptosis promoter, and prevented caspase3 cleavage, indicating that S1PR1 interfered with the mitochondrionassociated apoptotic processes in AML cells. In addition, the present study demonstrated that S1PR1 suppressed the generation of reactive oxygen species (ROS) in AML cells, and that the apoptosis mediated by the downregulation of S1PR1 was partially reversed by treatment with NacetylLcysteine, a ROS scavenging agent, suggesting that the S1PR1induced resistance of cell apoptosis resulted, at least partially, from the suppression of ROS generation. Additionally, S1PR1 was able to interfere with the signaling of cJun Nterminal kinase, which may have also contribute dto the suppression of cell apoptosis. By contrast, extracellular signalregulated kinase (ERK) signaling appeared to be positively modulated by the S1PR1induced enhancement of mitogenactivated protein kinase (MAPK) kinase 1 (MKK1) activation, suggesting that S1PR1 may promote cell survival and proliferation through enhancing the activation of MKK1ERK signaling. In conclusion, S1PR1 likely serves as an antiapoptotic/proproliferative protein in AML cells through the inhibition of mitochondrionassociated apoptosis and ROS generation, and via the regulation of multiple MAPK signaling cascades.
Assuntos
Apoptose , Proliferação de Células , Leucemia Mieloide Aguda/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Linhagem Celular Tumoral , Humanos , Leucemia Mieloide Aguda/patologia , MAP Quinase Quinase 1/metabolismo , Sistema de Sinalização das MAP Quinases , Espécies Reativas de Oxigênio/metabolismo , Receptores de Esfingosina-1-FosfatoRESUMO
This study was purposed to investigate the differences of cyto biological characteristics and protein expression levels between bortezomib-resistant T-lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and chemotherapeutic drugs to JurkatB5 cells (end selection concentration of bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and Jurkat cells were analyzed. The cell growth curves were drawn with viable cell counts by trypan blue assay, the colony formation rate were assayed by soft-agar colony culture, and the cell distributions in cell cycle were analyzed by flow cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP and MRP were measured by real-time fluorescence quantitative RT-PCR, the differences of protein expression levels were detected by SpringBio antibody microarray containing 720 proteins. The results showed that the drug resistance multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and JurkatB8 cells did not display significant cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no significant differences in the cell growth curve, colony formation rate and cell distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p > 0.05). There were no significant differences of mRNA expression levels of MDR1, LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable expression points detected by antibody microarray. Among them, 252 protein expression levels were not significantly different between JurkatB5, JurkatB8 and Jurkat cells (< 2-fold), including 15 drug resistance-related proteins. 12 proteins were detected at higher or lower expression levels in JurkatB5 or JurkatB8 cells then that in Jurkat cells (cell division cycle protein 34, cell division cycle protein 37, CD34 Type II, matrix metalloproteinase-2, tenascin, Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic acid receptor ß, integrin ß-1), but no proteins were detected in JurkatB5 and JurkatB8 cells with higher or lower expression levels than that in Jurkat cells. It is concluded that there are no significant differences in the characteristics of cellular biology between Jurkat and JurkatB with bortezomib-resistant and PSMB5 G322A mutation. There are no significant phenotype change of MDR and overexpression of genes related to MDR in PSMB5 mutated cells. There are no significantly differential expressions of a majority of known proteins related to drug resistance, tumor cells growth, proliferation, apoptosis, malignancy degree, aggressiveness.