scholarly journals Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome

Blood ◽  
2018 ◽  
Vol 132 (23) ◽  
pp. 2470-2483 ◽  
Author(s):  
Shiro Tara ◽  
Yusuke Isshiki ◽  
Yaeko Nakajima-Takagi ◽  
Motohiko Oshima ◽  
Kazumasa Aoyama ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Target Genes ◽  
Myeloproliferative Neoplasms ◽  
Lymphoblastic Leukemia ◽  
Transcriptional Profiling ◽  
Hoxa Cluster ◽  
Carboxyl Terminal ◽  
Regulator Genes ◽  
The Impact ◽  
P53 Target Genes

Abstract BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (BcorΔE4/y) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (BcorΔE9-10/y), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. BcorΔE9-10/y mice developed lethal T-ALL in a similar manner to BcorΔE4/y mice, whereas BcorΔE9-10/y hematopoietic cells showed a growth advantage in the myeloid compartment that was further enhanced by the concurrent deletion of Tet2. Tet2Δ/ΔBcorΔE9-10/y mice developed lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis, and the morphological dysplasia of blood cells. Tet2Δ/ΔBcorΔE9-10/y MDS cells reproduced MDS or evolved into lethal MDS/myeloproliferative neoplasms in secondary recipients. Transcriptional profiling revealed the derepression of myeloid regulator genes of the Cebp family and Hoxa cluster genes in BcorΔE9-10/y progenitor cells and the activation of p53 target genes specifically in MDS erythroblasts where massive apoptosis occurred. Our results reveal a tumor suppressor function of BCOR in myeloid malignancies and highlight the impact of Bcor insufficiency on the initiation and progression of MDS.

Role of the Polycomb Methyltransferase Ezh1 in Myelodysplastic Syndrome Induced By Ezh2 Insufficiency

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1968-1968
Author(s):  
Kazumasa Aoyama ◽  
Makiko Mochizuki-Kashio ◽  
Motohiko Oshima ◽  
Shuhei Koide ◽  
Yaeko Nakajima-Takagi ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Intraperitoneal Injection ◽  
Target Genes ◽  
Myeloproliferative Neoplasms ◽  
Hematologic Malignancies ◽  
Gene Set Enrichment Analysis ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Ezh1 and Ezh2, the catalytic components of polycomb-repressive complex 2 (PRC2), negatively control gene expression by catalyzing mono, di, and tri-methylation of histone H3 at lysine 27 (H3K27me1/me2/me3). Loss-of-function mutations of EZH2, but not those of EZH1, have been found in patients with hematologic malignancies such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and MDS/MPN overlap disorders. We previously demonstrated that hematopoietic cell-specific Ezh2 knockout mice (Ezh2Δ/Δ) developed hematologic malignancies including MDS and MDS/MPN. Although deletion of Ezh1, another enzymatic component of PRC2, (Ezh1-/-) did not significantly affect global H3K27me3 levels or hematopoiesis, deletion of both Ezh1 and Ezh2 in mice (Ezh1-/-Ezh2Δ/Δ) caused rapid exhaustion of hematopoietic stem cells (HSCs). Given that only Ezh1 and Ezh2 are known as enzymatic components of PRC2, we concluded that residual PRC2 enzymatic activity is required for HSC maintenance and development of hematologic malignancies in the setting of EZH2 insufficiency frequently observed in MDS. However, the role of Ezh1 in Ezh2-insufficient hematologic malignancies is still not fully understood since hematopoiesis could not be maintained in Ezh1-/-Ezh2Δ/Δ mice. Here we analyzed the impact of Ezh1 heterozygosity on Ezh2-null hematopoiesis (Ezh1+/-Ezh2Δ/Δ), in which PRC2 activity is mediated by a single allele of Ezh1, for better understanding of Ezh2-deficient hematologic malignancies. We first transplanted BM cells from Ezh1+/-Ezh2flox/flox CD45.2 mice with CD45.1 wild-type competitor cells into lethally irradiated CD45.1 recipient mice and deleted Ezh2 by intraperitoneal injection of tamoxifen. Ezh1+/-Ezh2Δ/Δ cells exhibited a lower repopulation capacity than Ezh2Δ/Δ but established persistent repopulation for at least 6 months after the deletion of Ezh2 while double knockout cells (Ezh1-/-Ezh2Δ/Δ) were outcompeted by competitor cells immediately. We next transplanted BM cells from Ezh1+/-Ezh2flox/flox CD45.2 mice without CD45.1 wild-type competitor cells into lethally irradiated CD45.1 recipient mice and deleted Ezh2 by intraperitoneal injection of tamoxifen. Importantly, recipient mice reconstituted with Ezh1+/-Ezh2Δ/Δ cells exhibited MDS-like phenotypes including anemia and morphological myelodysplasia, which were more pronounced than those of Ezh2Δ/Δ mice. Ezh1+/-Ezh2Δ/Δ mice also showed more advanced hematological abnormalities such as erythroid differentiation block, increased apoptosis of erythroid cells, and extramedullary hematopoiesis in the spleen than Ezh2Δ/Δ mice did. These results suggest that Ezh1 heterozygosity promotes the development of myelodysplasia in the setting of Ezh2insufficiency. Next we examined the molecular mechanism by which the loss of Ezh1 promotes myelodysplasia. Western blot and ChIP-sequence analyses revealed that global levels of H3K27me3 were not significantly changed but H3K27me3 levels at promoter regions of the PRC2 target genes were obviously reduced by Ezh1 heterozygosity in Ezh2Δ/Δ HSPCs. As a consequence, PRC2 target genes were highly de-repressed in Ezh1+/-Ezh2Δ/Δ LSK HSPCs compared with Ezh2Δ/Δ HSPCs. Among these, several genes appeared to be associated with MDS such as S100A9, encoding an inflammatory protein implicated in dyserythropoiesis in MDS. Furthermore, gene set enrichment analysis showed that the genes highly expressed in myeloid cells were positively enriched by Ezh1 heterozygosity in Ezh2Δ/ΔHSPCs. These findings indicate that dosage of Ezh1 is critical in the maintenance of Ezh2-insufficient hematopoiesis as well as the progression of MDS with Ezh2 insufficiency. Disclosures No relevant conflicts of interest to declare.

Identification of ERG Specific Target Genes by Genome-Wide Screening in T-Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3788-3788
Author(s):  
Liliana H Mochmann ◽  
Konrad Neumann ◽  
Juliane Bock ◽  
Jutta Ortiz Tanchez ◽  
Arend Bohne ◽  
...  
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Specific Treatment ◽  
P Value ◽  
Dna Templates ◽  
Genome Wide ◽  
A Genome ◽  
On Chip ◽  
T Cell Leukemogenesis ◽  
The Impact

Abstract The Ets related gene, ERG, encodes a transcription factor with a vital role in hematopoiesis. Recent findings have shown that ERG knockout mice require a minimum of one functional allele to ensure embryonic blood development and adult stem cell maintenance. Moreover, it was earlier reported that enforced expression of ERG induced oncogenic transformation in 3T3 cells. Overexpression of ERG, observed in a subset of acute T-lymphoblastic and acute myeloid leukemia patients, was associated with an inferior outcome. However, the impact of ERG contributing to this unfavourable phenotype has yet to be determined, as downstream targets of ERG in leukemia remain unknown. Herein, we conducted a genome-wide analysis of ERG target genes in T-lymphoblastic leukemia. Chromatin immunoprecipitation-on-chip array (ChIP-on-chip) analyses were performed using two ERG specific antibodies for the enrichment of ERG-bound DNA templates in T-lymphoblastic leukemia cells (Jurkat) with input DNA or IgG precipitated DNA as controls. Enriched DNA templates and control DNA were differentially labelled and co-hybridized to high resolution promoter chip arrays with 50–75mer probes (770,000) representing 29,000 annotated human transcripts (NimbleGen). Based on two independent ChIP-on-chip assays, bioinformatic analysis (ACME) yielded statistically significant enriched peaks (using a sliding window of 1000 bp, and a P-value < 0.0001) identifying promoter regions of 365 potential ERG target genes. From these genes, clustering by functional annotation was performed using the DAVID database and subsequently genes related to leukemia were further selected for quantitative PCR validation. The design of promoter primers included the highly conserved ETS GGAA DNA binding site. Genes with greater than two-fold enrichment (ERG ChIP versus control) included WNT2 (17-fold), OLIG2 (14-fold), WNT11 (7-fold), CCND1 (5-fold), WNT9A (4-fold), CD7 (3-fold), EPO (3-fold), ERBB4 (3-fold), RPBJL (3-fold), TRADD (3-fold), PIWIL1 (2-fold), TNFRSF25 (2-fold), TWIST1 (2-fold), and HDAC4 (2-fold). Interestingly, enriched target genes involved in developmental processes (WNT2, WNT9A, WNT11, TWIST1, PIWIL1, ERBB4, and OLIG2) have shown oncogenic potential when mutated or overexpressed. Thus, we hypothesize that overexpression of ERG may contribute to T-cell leukemogenesis by the deregulation of these oncogenic targets. Further disclosure of ERG directed downstream pathways may contribute to the design of specific treatment strategies (such as WNT inhibitors) with particular effectiveness in ERG deregulated leukemia.

scholarly journals The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1921 ◽  
Author(s):  
Olivier Mansier ◽  
Valérie Prouzet-Mauléon ◽  
Gwénaële Jégou ◽  
Kim Barroso ◽  
Diana Pelizzari Raymundo ◽  
...  
Keyword(s):  
Target Genes ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Janus Kinase ◽  
Expression Level ◽  
Mutant Proteins ◽  
Subsequent Activation ◽  
Induced Apoptosis ◽  
Er Homeostasis ◽  
The Impact

Background: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase – Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. Methods: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. Results: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. Conclusions: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes.

scholarly journals Influence of JAK2V617F allele burden on clinical phenotype of polycythemia vera patients: A study from India

2019 ◽  
Vol 08 (02) ◽  
pp. 127-129
Author(s):  
Sudha Sazawal ◽  
Kanwaljeet Singh ◽  
Sunita Chhikara ◽  
Rekha Chaubey ◽  
Manoranjan Mahapatra ◽  
...  
Keyword(s):  
Target Genes ◽  
Clinical Phenotype ◽  
Myeloproliferative Neoplasms ◽  
Treatment Protocol ◽  
Allele Burden ◽  
Downstream Target ◽  
Chronic Myeloproliferative Neoplasms ◽  
Enhanced Expression ◽  
The Impact ◽  
Jak2v617f Allele Burden

Abstract Background: Elevated JAK2V617F allele burden is associated with enhanced expression of downstream target genes in Philadelphia negative chronic myeloproliferative neoplasms (CMPNs) which include PV, ET & PMF. Previous studies have shown the impact of JAK2V617F allele burden on clinical phenotype of CMPNs. However, there is no data from India regarding the association between JAK2V617F allele burden and clinical phenotype in PV. Aims/Settings and Design: We aimed to investigate the effect of allele burden on clinical phenotype in 90 JAK2V617F positive PV patients and to see its influence on disease related complications. Material and Methods: Allele burden of 90 JAK2V617F positive PV patients was quantified by Real-time polymerase chain reaction (RQ-PCR). Results: 74/90 (82.22%) were males and 16/90 (17.78%) were females (median 45 years, range 35-78). Patients with age >50 years had significantly higher JAK2V617F allele burden (median 40.15%, range 0.49–91.62 %) than patients with ≤ 50 years age (median 48.59 %, range 0.56–86.74 %; P < 0.032). Patients with splenomegaly had significantly higher JAK2V617F allele burden (mean 50.24%, range 6.91–84.17%) than patients without splenomegaly (mean 33.82 %, range 0.49–71.83 %; P < 0.017). Patients with higher allele burden (median 57.20, range 43.4–72.03%) had significantly raised thrombotic events than the patients with lower allele burden (median 37.38, range 0.49–84.17% P < 0.043). 49/90 (54%) were homozygous and 41/90 (46%) were heterozygous. Conclusions: Higher JAK2V617F allele burden showed association with increased age, splenomegaly and thrombotic events. Thus, it may be considered for prognostication and setting up the treatment protocol in PV patients.

Transcriptional Profiling Identifies Genes Differentially Regulated by the BCR/ABL Fusion Oncogene.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1537-1537 ◽  
Author(s):  
Alexander Kohlmann ◽  
Claudia Schoch ◽  
Susanne Schnittger ◽  
Sylvia Merk ◽  
Martin Dugas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
Kinase Inhibitor ◽  
Protein Biosynthesis ◽  
Lymphoblastic Leukemia ◽  
Principal Component ◽  
Response To Therapy ◽  
Differentially Expressed ◽  
Hoxa Cluster

Abstract The translocation t(9;22) is associated with chronic myeloid leukemia (CML) and also occurs in 30% of adult acute lymphoblastic leukemia (ALL). In this study, we analyzed differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct phenotypes. Enriched monoculear cells from 218 adult patients were hybridized to Affymetrix U133 set (A+B) microarrays (discovery set). Resulting lists of differentially expressed genes were further analyzed in an independent set of 110 patients hybridized to U133 Plus 2.0 microarrays (validation set). In a first analysis ALL with t(9;22) (n=34 discovery, n=6 validation) and CML (n=75 discovery, n=49 validation) were included. Various unsupervised data analysis algorithms, e.g. hierarchical clustering and principal component analysis, clearly separated both types of t(9;22) leukemias from each other. A supervised approach, i.e. t-test statistics followed by false discovery rate estimation, identified genes that were significantly differentially expressed. Using the top differentially expressed genes in a classification algorithm (SVM) >97% of the samples were correctly assigned to their classes, both in the discovery and the validation cohort. This set of genes was further examined by pathway analysis (Ingenuity software). Numerous networks point at clear biological differences between both t(9;22) types. Higher expressed genes in CML were connected to networks related to leukotriene metabolism, immune response, integrin signaling, non-selective vesicle transport, or humoral defense mechanisms. This reflects the underlying transcriptional profile of granulation of promyelocytes in CML in contrast to the non-granulated immature ALL blasts. The aggressiveness of acute leukemic blasts is visualized by several pathways where genes with higher expression in t(9;22) positive ALL were aggregated to networks with cellular functions of DNA metabolism and replication, cell cycle progression, and protein biosynthesis. Next analyses were performed to mine for common t(9;22) target genes. CML samples were compared against an equal number of AML with normal karyotype, and t(9;22) ALL against an equal number of c-ALL/Pre-B-ALL without t(9;22). Then both lists of differentially expressed genes were compared for overlapping probe sets. Here, no statistically significant differentially expressed genes were identified as consistently associated with the presence of t(9;22) across the two lineages. In contrast, using a similar strategy where ALL and AML with t(11q23)/MLL were grouped together and were analyzed against various non-MLL positive leukemia subtypes it is possible to identify common t(11q23)/MLL target genes, e.g. a overexpressed HOXA cluster gene signature. This leads to the hypothesis that both types of t(9;22) leukemias, despite an identical underlying chromosomal aberration, trigger different genes involved in BCR/ABL-dependent leukemogenesis. Thus, depending on the cellular background, i.e. myeloid or lymphoid, translocation t(9;22) results in two types of leukemias with fundamental differences in gene expression, clinical course, and the time and quality of response to therapy which is demonstrated also if a BCR/ABL-specific tyrosine kinase inhibitor (e.g. imatinib mesylate) is administered.

Role of rs10406069 in miR-5196 in hyperdiploid childhood acute lymphoblastic leukemia

Epigenomics ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 1949-1955
Author(s):  
Angela Gutierrez-Camino ◽  
Chantal Richer ◽  
Pascal St-Onge ◽  
Elixabet Lopez-Lopez ◽  
Ana Carbone Bañeres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mirna Genes ◽  
Relevant Role ◽  
The Impact

Aim: To determine the role of single nucleotide polymorphisms (SNPs) in noncoding RNAs in childhood acute lymphoblastic leukemia (ALL) subtypes. Materials & methods: We screened all SNPs in 130 pre-miRNA genes to assess their role in the susceptibility of the most common subtypes of ALL: hyperdiploid and ETV6-RUNX1. Results: In two independent cohorts, we found a significant association between rs10406069 in miR-5196 and the risk of developing hyperdiploid ALL. This observation could be explained by the impact of the SNP on miR-5196 expression and in turn, in its target genes. Indeed, rs10406069 was associated with expression changes in SMC1A, a gene involved in sister chromatin cohesion. Conclusion: rs10406069 in miR-5196 may have a relevant role in hyperdiploid ALL risk.

scholarly journals Induced Transdifferentiation of Leukemia B-Cells to Macrophages Involves Reconfiguration of the DNA Methylome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5115-5115
Author(s):  
Alberto Bueno-Costa ◽  
David Piñeyro ◽  
Marta Soler ◽  
Biola Maria Javierre ◽  
José Angel Martínez-Climent ◽  
...  
Keyword(s):  
Dna Methylation ◽  
B Cells ◽  
Blood Cell ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Gene Promoters ◽  
Methylation Array ◽  
The Impact

Abstract The epigenomic changes that occur during the process of cellular differentiation, such as in the blood cell lineage, are currently not well understood, especially at distant regulatory regions such as enhancer sequences. To study the effects of DNA methylation on cellular (de)differentiation, we have used a human B Cell Acute Lymphoblastic Leukemia model of transdifferentiation (BLaER1), which has an estradiol-inducible CEBPA construct that allows the conversion of leukemic B cells to non-tumorigenic macrophage-like cells. By analyzing the DNA methylation landscape of these cells at different time points of transdifferentiation with an Illumina EPIC methylation array, we have found enhancer-associated CpGs that shifts their methylation levels at the end of the transdifferentiation. By merging these results with the data obtained by Genome-wide Chromosome Conformation Capture Capture (Hi-C) in naive B cells and macrophages, we studied the putative interaction between several gene-promoters and our differentially methylated CpGs. We then proceed further to characterize the impact of the observed interactions on gene expression. We have identified the DNA methylation dependent enhancer interactomes of B-cells and macrophages. These target genes are related with vesicle trafficking, endocytosis and immune response. Our data highlight the role of DNA methylation to determine cell identity in the blood cell lineage. Disclosures No relevant conflicts of interest to declare.

scholarly journals Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

2021 ◽  
Vol 22 (19) ◽  
pp. 10819
Author(s):  
Yoon-Young Kim ◽  
Kwang-Soo Kim ◽  
Yong-Jin Kim ◽  
Sung-Woo Kim ◽  
Hoon Kim ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Target Genes ◽  
Ovarian Tissue ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Regulatory Function ◽  
Tissue Samples ◽  
Mirna Sequencing ◽  
Regulator Genes ◽  
The Impact

Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

381: Promoter Hypermethylation Profile of Kidney Cancer with New Pro-Apoptotic P53 Target Genes and Possible Clinical Implications

2006 ◽  
Vol 175 (4S) ◽  
pp. 125-125
Author(s):  
Frank Christoph ◽  
Steffen Weikert ◽  
Carsten Kempkensteffen ◽  
Martin Schostak ◽  
Hans Krause ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Target Genes ◽  
Promoter Hypermethylation ◽  
Clinical Implications ◽  
P53 Target Genes

MicroRNAs and their role in hematological malignant diseases

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Cancer Tissue ◽  
Altered Expression ◽  
Diagnosis And Prognosis ◽  
Oncologic Patients ◽  
Different Types ◽  
Non Coding Rnas ◽  
Success Of Treatment ◽  
Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

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