Differential expression of microRNAs induced by trastuzumab emtansine (T-DM1) during megakaryocytopoiesis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 645-645 ◽  
Author(s):  
Hirdesh Uppal ◽  
Kaushiki Mahapatra ◽  
Sock-Cheng Lewin-Koh ◽  
Steven Olsen ◽  
Mark X. Sliwkowski ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Clinical Samples ◽  
Human Stem Cells ◽  
Antibody Drug Conjugate ◽  
Stem Loop ◽  
Real Time Analysis ◽  
Previously Treated ◽  
Grade 3

645 Background: Treatment with the HER2-targeted antibody–drug conjugate T-DM1 resulted in significantly longer PFS and OS vs lapatinib + capecitabine in patients previously treated with trastuzumab and a taxane in the phase 3 study EMILIA. Thrombocytopenia (TCP) was the dose-limiting toxicity for patients treated with T-DM1, although platelets do not express HER2. In EMILIA, grade 3/4 TCP was observed in 12.9% of T-DM1-treated patients. We have previously shown that T-DM1 inhibits megakaryocyte (Mk) production and differentiation. Here, we investigated the effect of T-DM1 on microRNAs (miRNAs) associated with megakaryocytopoiesis. Methods: Human stem cells (HSCs; CD133+/CD34+) from 8 donors were differentiated into Mks in the presence of T-DM1, trastuzumab, or vehicle. Total RNA was extracted using the miRNeasy MiniKit. cDNA was prepared using the Taqman miRNA RT Kit, FAM-MGB probes, and stem-loop RT primer pool set. miRNA expression was measured using the 96.96 Dynamic Array Chip on the Biomark HD Reader. Data were analyzed using Fluidigm real-time analysis software Spotfire 5, and SAS 9.2. hsa−let−7g and hsa−miR−671−3p were chosen as reference miRNAs due to their low variation between treatments and time points. Median normalization was also applied. Results: A total of 526 miRNA RT-qPCR assays were used to map miRNA expression during differentiation of HSCs from 8 separate donors to Mks in vitro over 30 days. Several miRNAs demonstrated temporal changes in their expression profiles during maturation, suggesting these miRNAs are potential drivers of Mk differentiation. T-DM1 treatment inhibited Mk production and differentiation. Concomitant modifications in the expression of specific miRNAs were observed. These modifications were not present in trastuzumab- or vehicle-treated cells, suggesting these miRNAs may be involved in the development of T-DM1–induced TCP. Conclusions: These results suggest that the miRNAs have the potential to be used as biomarkers for TCP in patients treated with T-DM1 and possibly other DM1 conjugates. Specific miRNA alterations related to T-DM1 treatment will be discussed following investigations using clinical samples to validate these preliminary data.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

scholarly journals MicroRNA Expression Profiles in Superficial Esophageal Squamous Cell Carcinoma before Endoscopic Submucosal Dissection: A Pilot Study

2021 ◽  
Vol 22 (9) ◽  
pp. 4789
Author(s):  
Shintaro Fujihara ◽  
Hideki Kobara ◽  
Noriko Nishiyama ◽  
Kayo Hirose ◽  
Hisakazu Iwama ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Endoscopic Submucosal Dissection ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Normal Tissues ◽  
Mirna Expression Profiles

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis when diagnosed at an advanced stage, and early detection and treatment are essential to improve survival. However, intraobserver and interobserver variation make the diagnosis of superficial ESCC difficult, and suitable biomarkers are urgently needed. Here, we compared the microRNA (miRNA) expression profiles of superficial ESCC tissues and adjacent normal tissues obtained immediately before esophageal endoscopic submucosal dissection. We found that ESCC and normal tissues differed in their miRNA expression profiles. In particular, miR-21-5p and miR-146b-5p were significantly upregulated and miR-210-3p was significantly downregulated in tumor tissues compared with normal tissues. We also detected significant associations between miRNA expression and ESCC invasion depth and lymphovascular invasion. The same differential expression of miR-21-5p, miR-146b-5p, and miR-210-3p was detected in ESCC cell lines compared with normal esophageal epithelial cells in vitro. However, transfection of ESCC cells with miR-210-3p and miR-21-5p mimics or inhibitors had partial effects on cell proliferation and invasion in vitro. These results indicate that miRNA expression is significantly deregulated in superficial ESCC, and suggest that the potential contribution of differentially expressed miRNAs to the malignant phenotype should be further investigated.

Monitoring Drug-Target Interactions through Target Engagement-Mediated Amplification on Arrays and in situ

2021 ◽  
Author(s):  
Rasel Al-Amin ◽  
Lars Johansson ◽  
Eldar Abdurakhmanov ◽  
Nils Landegren ◽  
Liza Löf ◽  
...  
Keyword(s):  
Drug Target ◽  
Kinase Inhibitors ◽  
Expression Profiles ◽  
Clinical Samples ◽  
Target Engagement ◽  
Rolling Circle Replication ◽  
Target Proteins ◽  
Dna Conjugates

Abstract Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to a panel of fixed adherent cells agreed with expectations from expression profiles of the cells. These findings were corroborated by competition experiments using kinase inhibitors with overlapping and non-overlapping target specificities, and translated to pathology tissue sections. We also introduce a proximity ligation variant of TEMA in which these drug-DNA conjugates are combined with antibody-DNA conjugates to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug-target interactions at spatial resolution in protein arrays, cells and tissues.

The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation

2021 ◽  
Author(s):  
Shan Yang ◽  
Wei Gao ◽  
Haoqi Wang ◽  
Xi Zhang ◽  
Yunzhe Mi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Clinical Samples

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 166-166 ◽  
Author(s):  
Denise Aysel Yardley ◽  
Ian E. Krop ◽  
Patricia LoRusso ◽  
Nicholas J. Robert ◽  
Musa Mayer ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Significant Activity ◽  
Bleeding Events ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Expanded Access ◽  
Previously Treated ◽  
Grade 3

166 Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1. Few T-DM1 data are available in settings approximating clinical practice. We present safety and efficacy data from T-PAS, an expanded access study of T-DM1 in patients (pts) with previously treated HER2-positive MBC. Methods: T-PAS is a US multicenter study of T-DM1 (3.6 mg/kg q3w) in HER2-positive (IHC 3+ or FISH/CISH+) locally advanced or MBC. Key eligibility criteria: prior anthracycline and taxane; prior capecitabine or 5-FU and ≥2 HER2-directed agents (including trastuzumab and lapatinib) for MBC; LVEF ≥50%. Primary endpoint: safety; secondary endpoint: investigator-assessed objective response rate (ORR) in pts with measurable disease. Safety was assessed on day 1 of each cycle; ECHO/MUGA scans were every 12 weeks. Results: This analysis includes 215 pts enrolled in May 2010–Sep 2011 (data cutoff 7/31/2012). Pts received a median of 7 prior systemic MBC therapies (range 1–23) with a median cumulative anthracycline dose of 240 mg/m2(range 6–2645). At baseline, median LVEF was 60% and 50% of pts had investigator-reported cardiovascular disease. Median follow-up was 5.9 months (range 0.1–25.3); median T-DM1 duration was 5.0 months (range 0–23) with 15.8% receiving >18 cycles. ORR was 25.6% (42/164). Rate of grade ≥3 AEs was 43.7% and of SAEs of any grade was 18.1%. Most common all-grade AEs were fatigue (50.7%), nausea (36.3%), and headache (24.2%). Most common grade ≥3 AEs were thrombocytopenia (7.9%), fatigue (4.7%), and increased aspartate aminotransferase and anemia (each 3.7%). There were no grade ≥3 bleeding events. Cardiac dysfunction (primarily asymptomatic decreases in LVEF) was reported in 8 pts (3.7%); 4 were grade ≥3, 3 resulting in T-DM1 discontinuation. Conclusions: In this study that more closely reflects the real-world setting, the safety profile of T-DM1 was similar to that previously reported in conventional clinical trials, with no new safety signals. In this pretreated population (median of 7 prior therapies for HER2-positive MBC), significant activity was observed. Clinical trial information: NCT01120561.

scholarly journals MicroRNAs in the Atherosclerotic Plaque

2013 ◽  
Vol 59 (12) ◽  
pp. 1708-1721 ◽  
Author(s):  
Emma Raitoharju ◽  
Niku Oksala ◽  
Terho Lehtimäki
Keyword(s):  
Atherosclerotic Plaque ◽  
Mirna Expression ◽  
Drug Targets ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Mirna Profile ◽  
In Vivo Studies ◽  
Atherosclerotic Plaques

BACKGROUND MicroRNAs (miRNA, miR) are noncoding RNAs that regulate gene expression by hindering translation. miRNA expression profiles have been shown to differ in vivo and in vitro in many cellular processes associated with cardiovascular diseases (CVDs). The progression of CVDs has also been shown to alter the blood miRNA profile in humans. CONTENT We summarize the results of animal and cell experiments concerning the miRNA profile in the atherosclerotic process and the changes which occur in the blood miRNA profile of individuals with CVD. We also survey the relationship of these CVD-related miRNAs and their expression in the human advanced atherosclerotic plaque, thereby providing more insight into miRNA function in human atherosclerotic lesions. The miRNAs miR-126, -134, -145, -146a, -198, -210, -340*, and -92a were found to be expressed differently in the blood of individuals affected and unaffected by CVD. These differences paralleled those seen in tissue comparisons of miRNA expression in advanced atherosclerotic plaques and healthy arteries. Furthermore, several miRNAs associated with atherosclerosis in in vitro studies (such as miR-10a, -126, -145, -146a/b, -185, -210, and -326) were expressed in plaques in a similar pattern as was predicted by the in vitro experiments. The clinical implications of miRNAs in atherosclerosis as biomarkers and as possible drug targets are also reviewed. SUMMARY miRNA profiles in in vitro and in vivo studies as well as in human peripheral blood are quite representative of the miRNA expression in human atherosclerotic plaques. miRNAs appear promising in terms of future clinical applications.

scholarly journals Effects of Short-time Exposure to Atrazine on miRNA Expression Profiles in the Gonad of Common Carp (Cyprinus carpio)

2018 ◽  
Author(s):  
Fang Wang ◽  
Qian-wen Yang ◽  
Wen-Jie Zhao ◽  
Qi-Yan Du ◽  
Zhong-Jie Chang
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Endocrine Disrupting Chemical ◽  
Endocrine Disrupting ◽  
Mirna Expression Profiles

ABSTRACTMicroRNAs (miRNAs) are endogenous small non-coding RNAs that negatively regulate gene expression by targeting specific mRNAs; they are involved in the modulation of important mRNA networks involved in toxicity. Atrazine is a known endocrine-disrupting chemical, whose molecular mechanisms are unknown. In this study, common carp (Cyprinus carpio) gonads at two key developmental stages were exposed to 0.428 ppb atrazine for 24 h in vitro. MiRNA expression profiles were analysed to identify miRNAs related to gonad development and to reveal the atrazine mechanisms interfering with gonad differentiation. Atrazine exposure caused significant alteration of multiple miRNAs. Compared with the juvenile ovary, more miRNAs were down-regulated in juvenile testis, some of these down-regulated miRNAs target the steroid hormone biosynthesis pathway related-genes. Predicted target genes of differently-expressed miRNAs after exposure to atrazine were involved in many reproductive biology signalling pathways. We suggest that these target genes may have important roles in atrazine-induced reproductive toxicity by altering miRNAs expression. Our results also indicate that atrazine can up-regulate aromatase expression through miRNAs, which supports the hypothesis that atrazine has endocrine-disrupting activity by altering the expression of genes of the Hypothalamus-Pituitary-Gonad axis through its corresponding miRNAs. This study tells us the following conclusions: 1. Atrazine exposure results in significant alterations of miRNAs whose predicted target genes are associated with reproductive processes. 2. In the primordial gonad, atrazine promoted the expression of early gonad-determining genes by decreasing specific miRNAs. 3. In the juvenile gonad, atrazine promoted the biosynthesis of steroid hormones.

scholarly journals Differential Leukocyte miRNA Responses Following Pan T Cell, Allorecognition and Allosecretome-Based Therapeutics Activation

2019 ◽  
Author(s):  
Xining Yang ◽  
Wendy M. Toyofuku ◽  
Mark D. Scott
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
T Cell Activation ◽  
Mirna Expression ◽  
Cell Activation ◽  
Expression Profiles ◽  
Immunomodulatory Activity ◽  
Mirna Expression Profiles

Abstract Background: Effective immunomodulation of T cell responses is critical in treating both autoimmune diseases and cancer. Our previous studies have demonstrated that nanoscale bioengineering of cell surfaces with methoxypolyethylene glycol (mPEG) induces a potent tolerogenic immunomodulatory effect. Moreover, secretomes derived from mPEG- or control mixed lymphocyte alloactivation assays also exerted potent immunomodulatory activity that was mediated by microRNAs (miRNA). In this study, the immunomodulatory effects of Pan T cell activators (PHA and anti-CD3/CD28), alloactivation (MHC-disparate donors; ± mPEG grafting) and biomanufactured miRNA-based allo-secretome therapeutics (SYN, TA1, IA1 and IA2) were examined on T cell proliferation, subset differentiation and leukocyte miRNA expression profiles of resting human PBMC. Results: In contrast to Pan T cell activation, allorecognition and the pro-inflammatory IA1 secretome product induced increasingly controlled proliferation of resting PBMC. The differential effects of the activation strategies were also apparent in T cell differentiation and the Teff:Treg ratio and in the miRNA expression profiles noted in the treated PBMC. In contrast, the mPEG-PBMC and TA1 secretome products inhibited alloproliferation. Importantly, the activation strategies exerted significantly different miRNA expression in the treated leukocytes that was associated with differences in proliferation and cellular differentiation. Conclusions: Immunomodulatory secretome-derived, miRNA-enriched, therapeutics can be reproducibly biomanufactured that will induce the specific bioregulatory events necessary to induce the differentiation of naïve T cells to produce a tolerogeneic (TA1) or inflammatory (IA1) response both in vitro and in vivo. The successful development and biomanufacturing of immunomodulatory, miRNA-enriched, secretome biotherapeutics may provide potent tools for the systemic treatment of autoimmune diseases or enhancing the endogenous immune response to cancer while reducing the potential adverse risks of more non-specific immunomodulatory approaches.

Comparing mRNA and sncRNA profiles during the maternal-to-embryonic transition in bovine IVF and scNT embryos

2021 ◽  
Author(s):  
Jocelyn M Cuthbert ◽  
Stewart J Russell ◽  
Irina A Polejaeva ◽  
Qinggang Meng ◽  
Kenneth L White ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Developmental Competence ◽  
Messenger Rnas ◽  
Aberrant Expression ◽  
Rna Transcripts ◽  
Mrna Targets ◽  
Mirna Expression Profiles

Abstract Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved.

MiRNA Expression Signatures in Acute Myeloid Leukemia Are Predictors for Patient Outcome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 152-152
Author(s):  
Thomas Illmer ◽  
David Kosel ◽  
Markus A. Schaich ◽  
Christian Thiede ◽  
Andreas Neubauer ◽  
...  
Keyword(s):  
Microarray Data ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Stem Cell Differentiation ◽  
Chromosome 7 ◽  
Differentially Expressed ◽  
Specific Expression ◽  
Monosomy 7 ◽  
Median Expression

Abstract Only recently, a class of gene regulatory molecules (miRNA’s) has been described that have the potential for posttranscriptional and translational gene regulation. MiRNA’s can influence critical cellular properties like proliferation and differentiation. Since these properties vary substantially in genetically defined AML subsets we have chosen to analyze AML patients with inv(16) (n=12); standard risk cytogenetic classification (mainly comprising the normal karyotype) (SR) (n=21) and with monosomy 7 or deletion7q (n=17) using DNA oligonucleotide arrays which are employing the mirVANA miRNA probe set. Principal Component Analysis (PCA) of AML samples from patients with inv(16) showed only minor differences to normal bone marrow (BM). In contrast AML patients with SR could be clearly divided in two subgroups - one subgroup that showed miRNA expression pattern close to BM and a distinctly different subgroup. Comparison of SR patient samples with BM using ANOVA tests revealed 9 differentially expressed miRNA’s (mir-223; mir-15a; mir-16; mir-203; mir-103; mir-23b; mir-107, mir-17–5p and mir23a). AML patients with aberrations of chromosome 7 showed highly distinct PCA pattern as compared to BM samples. 64 miRNA’s were found to be differentially expressed in those patients as compared to BM. All miRNA’s located on chromosome7 that were included in the array were found downregulated in AML patients with aberrant chromosome 7 (e.g.mir-335). To further substantiate the microarray data we analyzed a total of 108 AML patients with inv(16), SR cytogenetics and aberrations of chromosome 7 for mir-23a, mir-223, mir-16 and mir-335 expression by qRT-PCR. Supporting the microarray data it could be shown that the median expression levels of mir-23a, mir-223 and mir-16 were lowest in patients with SR cytogenetics, whereas AML patients with chromosome 7 aberrations showed lowest median expression for mir-335 transcripts. This was in clear contrast to the expression of mir-150, a miRNA which could be previously shown to associate with immature T-cells and which had the highest expression in AML samples with chromosome 7 aberrations. Expression of mir-150 was correlated with a high CD34 percentage in the investigated AML samples (p<0.001) whereas mir-223 did not correlate with CD34 but was strongly associated with the surface expression of CD14 (p<0.001). In an in-vitro model of G-CSF induced CD34+ stem cell differentiation mir-223 and mir-16 were slightly upregulated whereas mir-150 disappeared during the process of differentiation. Finally, the investigated miRNA were entered in a model for outcome prediction in AML samples with SR cytogenetics including known risk factors. Within this model the ratio of mutant vs. wt FLT-3 was the strongest predictor of overall survival (p<0.01). Additonally, mir-23a expression proved to be an independent negative prognostic factor for AML patients with SR cytogenetics (p<0.05). In conclusion, the presented data demonstrate specific expression profiles of miRNA’s in AML patients with different cytogenetic risk profiles. As it could be shown for patients with SR cytogenetics the observed expression profiles are likely to contribute to a deregulated differentiation and may influence therapeutic outcome.

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