scholarly journals An RpoHI-Dependent Response Promotes Outgrowth after Extended Stationary Phase in the Alphaproteobacterium Rhodobacter sphaeroides

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
B. Remes ◽  
T. Rische-Grahl ◽  
K. M. H. Müller ◽  
K. U. Förstner ◽  
Sung-Huan Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stationary Phase ◽  
Rhodobacter Sphaeroides ◽  
Growth Phase ◽  
Stress Responses ◽  
Cell Number ◽  
Sigma Factors ◽  
Fold Change ◽  
Regulatory Mechanisms ◽  
Altered Expression

ABSTRACT Under unfavorable growth conditions, bacteria enter stationary phase and can maintain cell viability over prolonged periods with no increase in cell number. To obtain insights into the regulatory mechanisms that allow bacteria to resume growth when conditions become favorable again (outgrowth), we performed global transcriptome analyses at different stages of growth for the alphaproteobacterium Rhodobacter sphaeroides. The majority of genes were not differentially expressed across growth phases. After a short stationary phase (about 20 h after growth starts to slow down), only 7% of the genes showed altered expression (fold change of >1.6 or less than −1.6, corresponding to a log2 fold change of >0.65 or less than −0.65, respectively) compared to expression at exponential phase. Outgrowth induced a distinct response in gene expression which was strongly influenced by the length of the preceding stationary phase. After a long stationary phase (about 64 h after growth starts to slow down), a much larger number of genes (15.1%) was induced in outgrowth than after a short stationary phase (1.7%). Many of those genes are known members of the RpoHI/RpoHII regulons and have established functions in stress responses. A main effect of RpoHI on the transcriptome in outgrowth after a long stationary phase was confirmed. Growth experiments with mutant strains further support an important function in outgrowth after prolonged stationary phase for the RpoHI and RpoHII sigma factors. IMPORTANCE In natural environments, the growth of bacteria is limited mostly by lack of nutrients or other unfavorable conditions. It is important for bacterial populations to efficiently resume growth after being in stationary phase, which may last for long periods. Most previous studies on growth-phase-dependent gene expression did not address outgrowth after stationary phase. This study on growth-phase-dependent gene regulation in a model alphaproteobacterium reveals, for the first time, that the length of the stationary phase strongly impacts the transcriptome during outgrowth. The alternative sigma factors RpoHI and RpoHII, which are important regulators of stress responses in alphaproteobacteria, play a major role during outgrowth following prolonged stationary phase. These findings provide the first insight into the regulatory mechanisms enabling efficient outgrowth.

scholarly journals Involvement of microRNA in Solid Cancer: Role and Regulatory Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 343
Author(s):  
Ying-Chin Lin ◽  
Tso-Hsiao Chen ◽  
Yu-Min Huang ◽  
Po-Li Wei ◽  
Jung-Chun Lin
Keyword(s):  
Gene Expression ◽  
Regulatory Mechanism ◽  
Transcriptional Factor ◽  
Regulatory Mechanisms ◽  
Solid Cancer ◽  
Detailed Knowledge ◽  
Altered Expression ◽  
Human Malignancy ◽  
Regulated Expression ◽  
Pivotal Mechanism

MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer.

scholarly journals Genetic Evidence that Legionella pneumophila RpoS Modulates Expression of the Transmission Phenotype in Both the Exponential Phase and the Stationary Phase

2004 ◽  
Vol 72 (5) ◽  
pp. 2468-2476 ◽  
Author(s):  
Michael A. Bachman ◽  
Michele S. Swanson
Keyword(s):  
Life Cycle ◽  
Rna Polymerase ◽  
Stationary Phase ◽  
Growth Phase ◽  
Legionella Pneumophila ◽  
Opportunistic Pathogen ◽  
Sigma Factors ◽  
Exponential Phase ◽  
Posttranscriptional Control ◽  
Multiple Copies

ABSTRACT The opportunistic pathogen Legionella pneumophila alternates between two states: replication within phagocytes and transmission between host amoebae or macrophages. In broth cultures that model this life cycle, during the replication period, CsrA inhibits expression of transmission traits. When nutrients become limiting, the alarmone (p)ppGpp accumulates and the sigma factors RpoS and FliA and the positive activators LetA/S and LetE promote differentiation to the transmissible form. Here we show that when cells enter the postexponential growth phase, RpoS increases expression of the transmission genes fliA, flaA, and mip, factors L. pneumophila needs to establish a new replication niche. In contrast, in exponential (E)-phase cells whose (p)ppGpp levels are low, rpoS inhibits expression of transmission traits, on the basis of three separate observations. First, rpoS RNA levels peak in the E phase, suggestive of a role for RpoS during replication. Second, in multiple copies, rpoS decreases the amounts of csrA, letE, fliA, and flaA transcripts and inhibits the transmission traits of motility, infectivity, and cytotoxicity. Third, rpoS blocks expression of cytotoxicity and motility by E-phase bacteria that have been induced to express the LetA activator ectopically. The data are discussed in the context of a model in which the alarmone (p)ppGpp enables RpoS to outcompete other sigma factors for binding to RNA polymerase to promote transcription of transmission genes, while LetA/S acts in parallel to relieve CsrA posttranscriptional repression of the transmission regulon. By coupling transcriptional and posttranscriptional control pathways, intracellular L. pneumophila could respond to stress by rapidly differentiating to a transmissible form.

scholarly journals Transcriptome profiling of Variovorax paradoxus EPS under different growth conditions reveals regulatory and structural novelty in biofilm formation

2019 ◽  
Author(s):  
Richard J. Fredendall ◽  
Jenny L. Stone ◽  
Michael J. Pehl ◽  
Paul M. Orwin
Keyword(s):  
Gene Expression ◽  
Stationary Phase ◽  
Exponential Growth ◽  
Biofilm Formation ◽  
Extracellular Dna ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Stationary Phase Culture ◽  
Altered Expression ◽  
Variovorax Paradoxus

ABSTRACTWe used transcriptome analysis by paired-end strand specific RNA-seq to evaluate the specific changes in gene expression associated with the transition to static biofilm growth in the rhizosphere plant growth promoting bacterium Variovorax paradoxus EPS. Triplicate biological samples of exponential growth, stationary phase, and static biofilm samples were examined. DESeq2 and Rockhopper were used to identify robust and widespread shifts in gene expression the transcriptomic signals specific to each growth phase. Weidentified 1711 protein coding genes (28%) using DESeq2 that had altered expression greater than 2-fold specifically in biofilms compared to exponential growth. Fewer genes were specifically differentially expressed in stationary phase culture (757, 12%). A small set of genes (103/6020) were differentially expressed in opposing fashions in biofilm and stationary phase, indicating potentially substantial shifts in phenotype. Gene Ontology analysis showed that the only class of genes specifically upregulated in biofilms were associated with nutrient transport, highlighting the importance of nutrient uptake in the biofilm. The biofilm specific genes did not overlap substantially with the loci identified by mutagenesis studies, although some were present in both sets. The most highly upregulated biofilm specific gene is predicted to be a part of the RNA degradosome, which indicates that RNA stability is used to regulate the biofilm phenotype. Two small putative proteins, Varpa_0407 and Varpa_3832, are highly expressed specifically in biofilms and are predicted to be secreted DNA binding proteins, that may stabilize extracellular DNA as a component of the biofilm matrix. An flp/tad type IV pilus locus (Varpa_5148-60) is strongly downregulated in specifically in biofilms, in contrast with results from other systems for these pili. Mutagenesis confirms that this locus is important in surface motility rather than biofilm formation. These experimental results suggest that V. paradoxus EPS biofilms have substantial regulatory and structural novelty.

scholarly journals Characterization of cold stress responses in different rapeseed ecotypes based on metabolomics and transcriptomics analyses

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8704 ◽  
Author(s):  
Hongju Jian ◽  
Ling Xie ◽  
Yanhua Wang ◽  
Yanru Cao ◽  
Mengyuan Wan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Cold Stress ◽  
Stress Responses ◽  
Differentially Expressed ◽  
Regulatory Mechanisms ◽  
Primary Metabolites ◽  
Stress Treatment ◽  
Organic Acids And Sugars

The winter oilseed ecotype is more tolerant to low temperature than the spring ecotype. Transcriptome and metabolome analyses of leaf samples of five spring Brassica napus L. (B. napus) ecotype lines and five winter B. napus ecotype lines treated at 4 °C and 28 °C were performed. A total of 25,460 differentially expressed genes (DEGs) of the spring oilseed ecotype and 28,512 DEGs of the winter oilseed ecotype were identified after cold stress; there were 41 differentially expressed metabolites (DEMs) in the spring and 47 in the winter oilseed ecotypes. Moreover, more than 46.2% DEGs were commonly detected in both ecotypes, and the extent of the changes were much more pronounced in the winter than spring ecotype. By contrast, only six DEMs were detected in both the spring and winter oilseed ecotypes. Eighty-one DEMs mainly belonged to primary metabolites, including amino acids, organic acids and sugars. The large number of specific genes and metabolites emphasizes the complex regulatory mechanisms involved in the cold stress response in oilseed rape. Furthermore, these data suggest that lipid, ABA, secondary metabolism, signal transduction and transcription factors may play distinct roles in the spring and winter ecotypes in response to cold stress. Differences in gene expression and metabolite levels after cold stress treatment may have contributed to the cold tolerance of the different oilseed ecotypes.

scholarly journals Complex Physiology and Compound Stress Responses during Fermentation of Alkali-Pretreated Corn Stover Hydrolysate by an Escherichia coli Ethanologen

2012 ◽  
Vol 78 (9) ◽  
pp. 3442-3457 ◽  
Author(s):  
Michael S. Schwalbach ◽  
David H. Keating ◽  
Mary Tremaine ◽  
Wesley D. Marner ◽  
Yaoping Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Amino Acids ◽  
Stationary Phase ◽  
Gene Expression Profiling ◽  
Stress Responses ◽  
Expression Profiling ◽  
Content Type ◽  
E Coli ◽  
Cell Maintenance

ABSTRACTThe physiology of ethanologenicEscherichia coligrown anaerobically in alkali-pretreated plant hydrolysates is complex and not well studied. To gain insight into howE. coliresponds to such hydrolysates, we studied anE. coliK-12 ethanologen fermenting a hydrolysate prepared from corn stover pretreated by ammonia fiber expansion. Despite the high sugar content (∼6% glucose, 3% xylose) and relatively low toxicity of this hydrolysate,E. coliceased growth long before glucose was depleted. Nevertheless, the cells remained metabolically active and continued conversion of glucose to ethanol until all glucose was consumed. Gene expression profiling revealed complex and changing patterns of metabolic physiology and cellular stress responses during an exponential growth phase, a transition phase, and the glycolytically active stationary phase. During the exponential and transition phases, high cell maintenance and stress response costs were mitigated, in part, by free amino acids available in the hydrolysate. However, after the majority of amino acids were depleted, the cells entered stationary phase, and ATP derived from glucose fermentation was consumed entirely by the demands of cell maintenance in the hydrolysate. Comparative gene expression profiling and metabolic modeling of the ethanologen suggested that the high energetic cost of mitigating osmotic, lignotoxin, and ethanol stress collectively limits growth, sugar utilization rates, and ethanol yields in alkali-pretreated lignocellulosic hydrolysates.

Oxidoreductase, morphogenesis, extracellular matrix, and calcium ion-binding gene expression in streptozotocin-induced diabetic rat heart

2007 ◽  
Vol 293 (3) ◽  
pp. E759-E768 ◽  
Author(s):  
Erik van Lunteren ◽  
Michelle Moyer
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Calcium Ion ◽  
Ion Homeostasis ◽  
Fold Change ◽  
Diabetic Rat ◽  
Ion Binding ◽  
Oxidoreductase Activity ◽  
Altered Expression ◽  
Calcium Ion Binding

Diabetes has far-ranging effects on cardiac structure and function. Previous gene expression studies of the heart in animal models of type 1 diabetes concur that there is altered expression of genes involved in lipid and protein metabolism, but they diverge with regard to expression changes involving many other functional groups of genes of mechanistic importance in diabetes-induced cardiac dysfunction. To obtain additional information about these controversial areas, genome-wide expression was assessed using microarrays in left ventricle from streptozotocin-diabetic and normal rats. There were 261 genes with statistically significant altered expression of at least ±1.5-fold, of which 124 were increased and 137 reduced by diabetes. Gene ontology assignment testing identified several statistical significantly overrepresented groups among genes with altered expression, which differed for increased compared with reduced expression. Relevant gene groups with increased expression by diabetes included lipid metabolism ( P < 0.001, n = 13 genes, fold change 1.5 to 14.6) and oxidoreductase activity ( P < 0.001, n = 17, fold change 1.5 to 4.6). Groups with reduced expression by diabetes included morphogenesis ( P < 0.00001, n = 28, fold change −1.5 to −5.1), extracellular matrix ( P < 0.02, n = 9, fold change −1.5 to −3.9), cell adhesion ( P < 0.05, n = 10, fold change −1.5 to −2.7), and calcium ion binding ( P < 0.01, n = 13, fold change −1.5 to −3.0). Array findings were verified by quantitative PCR for 36 genes. These data combined with previous findings strengthen the evidence for diabetes-induced cardiac gene expression changes involved in cell growth and development, oxidoreductase activity, and the extracellular matrix and also point out other gene groups not previously identified as being affected, such as those involved in calcium ion homeostasis.

Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs

2007 ◽  
Vol 29 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Caroline Ojaimi ◽  
Khaled Qanud ◽  
Thomas H. Hintze ◽  
Fabio A. Recchia
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Fold Change ◽  
Differentially Expressed ◽  
Altered Expression ◽  
Cardiac Decompensation ◽  
Number Of Genes ◽  
End Stage

Our aim was to determine the changes in the gene expression profile occurring during the transition from compensated dysfunction (CD) to decompensated heart failure (HF) in pacing-induced dilated cardiomyopathy. Twelve chronically instrumented dogs underwent left ventricular pacing at 210 beats/min for 3 wk and at 240 beats thereafter, and four normal dogs were used as control. The transition from CD to HF occurred between the 3rd and 4th wk of pacing, with end-stage HF at 28 ± 1 days. RNA was extracted from left ventricular tissue at control and 3 and 4 wk of pacing ( n = 4) and tested with the Affymetrix Canine Array. We found 509 genes differentially expressed in CD vs. control ( P ≤ 0.05, fold change ≥±2), with 362 increasing and 147 decreasing; 526 genes were differentially expressed in HF vs. control ( P ≤ 0.05; fold change ≥±2), with 439 increasing and 87 decreasing. To better understand the transition, we compared gene alterations at 3 vs. 4 wk pacing and found that only 30 genes differed ( P ≤ 0.05; fold change of ±2). We conclude that a number of processes including normalization of gene regulation during decompensation, appearance of new upregulated genes and maintenance of gene expression all contribute to the transition to overt heart failure with an unexpectedly small number of genes differentially regulated.

scholarly journals Network rewiring: physiological consequences of reciprocally exchanging the physical locations and growth-phase-dependent expression patterns of the Salmonella fis and dps genes

2020 ◽  
Author(s):  
Marina M Bogue ◽  
Aalap Mogre ◽  
Michael C Beckett ◽  
Nicholas R Thomson ◽  
Charles J Dorman
Keyword(s):  
Gene Expression ◽  
Protein Binding ◽  
Stationary Phase ◽  
Growth Phase ◽  
Regulatory Network ◽  
Mammalian Cells ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Exponential Phase ◽  
Virulence Gene Expression

ABSTRACTThe Fis nucleoid-associated protein controls the expression of a large and diverse regulon of genes in Gram-negative bacteria. Fis production is normally maximal in bacteria during the early exponential phase of batch culture growth, becoming almost undetectable by the onset of stationary phase. We tested the effect on the Fis regulatory network in Salmonella of moving the complete fis gene from its usual location near the origin of chromosomal replication to the position normally occupied by the dps gene in the Right macrodomain of the chromosome, and vice versa, creating the strain GX. In a parallel experiment, we tested the effect of rewiring the Fis regulatory network by placing the fis open reading frame under the control of the stationary-phase-activated dps promoter at the dps genetic location within Ter, and vice versa, creating the strain OX. ChIP-seq was used to measure global Fis protein binding and gene expression patterns. Strain GX showed few changes when compared with the wild type, although we did detect increased Fis binding at Ter, accompanied by reduced binding at Ori. Strain OX displayed a more pronounced version of this distorted Fis protein-binding pattern together with numerous alterations in the expression of genes in the Fis regulon. OX, but not GX, had a reduced ability to infect cultured mammalian cells. These findings illustrate the inherent robustness of the Fis regulatory network to rewiring based on gene repositioning alone and emphasise the importance of fis expression signals in phenotypic determination.IMPORTANCEWe assessed the impacts on Salmonella physiology of reciprocally translocating the genes encoding the Fis and Dps nucleoid-associated proteins (NAPs), and of inverting their growth phase production patterns such that Fis is produced in stationary phase (like Dps) and Dps is produced in exponential phase (like Fis). Changes to peak binding of Fis were detected by ChIP-seq on the chromosome, as were widespread impacts on the transcriptome, especially when Fis production mimicked Dps. Virulence gene expression and the expression of a virulence phenotype were altered. Overall, these radical changes to NAP gene expression were well tolerated, revealing the robust and well-buffered nature of global gene regulation networks in the bacterium.

scholarly journals Identification of Conserved, RpoS-Dependent Stationary-Phase Genes of Escherichia coli

1998 ◽  
Vol 180 (23) ◽  
pp. 6283-6291 ◽  
Author(s):  
Herb E. Schellhorn ◽  
Jonathon P. Audia ◽  
Linda I. C. Wei ◽  
Lily Chang
Keyword(s):  
Escherichia Coli ◽  
Stationary Phase ◽  
Growth Phase ◽  
Regulatory Mechanisms ◽  
Alternative Sigma Factor ◽  
Gram Negative Bacteria ◽  
Gene Fusions ◽  
Free Living ◽  
Cellular Resistance ◽  
Regulated Functions

ABSTRACT During entry into stationary phase, many free-living, gram-negative bacteria express genes that impart cellular resistance to environmental stresses, such as oxidative stress and osmotic stress. Many genes that are required for stationary-phase adaptation are controlled by RpoS, a conserved alternative sigma factor, whose expression is, in turn, controlled by many factors. To better understand the numbers and types of genes dependent upon RpoS, we employed a genetic screen to isolate more than 100 independent RpoS-dependent gene fusions from a bank of several thousand mutants harboring random, independent promoter-lacZ operon fusion mutations. Dependence on RpoS varied from 2-fold to over 100-fold. The expression of all fusion mutations was normal in an rpoS/rpoS +merodiploid (rpoS background transformed with anrpoS-containing plasmid). Surprisingly, the expression of many RpoS-dependent genes was growth phase dependent, albeit at lower levels, even in an rpoS background, suggesting that other growth-phase-dependent regulatory mechanisms, in addition to RpoS, may control postexponential gene expression. These results are consistent with the idea that many growth-phase-regulated functions inEscherichia coli do not require RpoS for expression. The identities of the 10 most highly RpoS-dependent fusions identified in this study were determined by DNA sequence analysis. Three of the mutations mapped to otsA, katE,ecnB, and osmY—genes that have been previously shown by others to be highly RpoS dependent. The six remaining highly-RpoS-dependent fusion mutations were located in other genes, namely, gabP, yhiUV, o371,o381, f186, and o215.

Analysis Of Leukemic Stem Cell Population Comparing NPM1wt and NPM1mut AML Patients and Potential Therapeutic Targets

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2624-2624
Author(s):  
Vanessa Schneider ◽  
Lars Bullinger ◽  
Lu Zhang ◽  
Markus Rojewski ◽  
Markus Wiesneth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Cell Sorting ◽  
Cell Number ◽  
Fold Change ◽  
Expression Level ◽  
Immunocytochemical Staining ◽  
Stem Cell Population ◽  
Npm1 Mutation ◽  
Prognostic Features

Abstract Treatment of acute myeloid leukemia (AML) patients became more effective, yet the relapse rate is still high and cure rate still low. Different therapeutic approaches, based on molecular targeting are offering new treatment strategies using markers like FLT3, NPM1, cKIT and DNMT3A. Many others are currently under investigation. Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment. Therefore LSC represent a critical target for further therapeutic options. AML with mutated nucleophosmin (NPM1) gained attention because of its distinctive molecular, clinical, and prognostic features. NPM1 mutation is also an interesting target for specific immunotherapy (Greiner et al., Blood 2012), however LSC of this new entity have not been completely characterized. Differentially expressed genes might influence molecular and immunological relevant pathways which could have an impact on the better overall survival of the mutated patients. In this study, we were interested in expression differences of the LSC enriched cell fraction descendent of NPM1wt and NPM1mut primary AML patients. We suggest that expression differences between the patients groups could be a factor for the better overall survival of NPM1mut patients. In addition we aimed to study new targets on NPM1mut LSC for new therapeutical purposes. We enriched the CD34+CD38- fraction of primary AML peripheral blood mononuclear cells (PBMC), by Fluorescence-activated cell sorting (FACS) and Magnetic-activated cell sorting (MACS), comparing both methods in efficiency and feasibility. We chose FACS for further enrichment assays, as it resulted in a mean purity of 92% vs 88% using MACS, and a higher cell number after sorting (9% more) in the first pilot trials. We sorted 21 AML patient samples; 12 NPM1wt and 9 NPM1mut. We also enriched healthy donor samples for HSC purification using FACS, in order to compare expression levels. We showed that enriched CD34+CD38- cells in NPM1mut AML samples harbor cytoplasmic NPM1 via immunocytochemical staining, indicating that these cells belong to the leukemic clone. The cell number and RNA quality was sufficient for further Microarray studies in which we analysed the CD34+CD38- enriched compartments descendent from NPM1mut and NPM1wt patients. Those showed significant differences in gene expression patterns which noticeably are immunologically coined, for example: immunoglobulin superfamily, member 10 (p = 0.0003405; fold change: 6.22) and the interleukin 12 receptor, beta 1 (p = 0.000834, fold change: 1.87). This impression was confirmed by pathway analysis indicating deregulation of pathways like the NO2-dependent IL 12 Pathway in NK cells and the Th1/Th2 Differentiation and the Platelet Amyloid Precursor Protein Pathway. Functional assays, confirming the biological importance of these factors have been performed for example an assay to test the effect of IL12 on AML cellines. Furthermore we screened our data for new potential therapeutic target structures, specifically on enriched CD34+CD38- cells of NPM1mut patients, comparing the expression level of target genes to NPM1wt CD34+CD38- cells, and the expression level on HSC. Amongst others, our most promising candidates are SERPINA1 (p = 0.0062344, fold change: 14.32), OSCAR (p = 6.11E-05, fold change: 9.03) and several further interesting genes. These genes could be used in order to target CD34+CD38- cells of NPM1mut patients in a therapeutic manner. Taken together, we successfully enriched the CD34+CD38- fraction of NPM1mut and NPM1wt AML patients and performed Microarray analysis, unraveling gene expression differences between the two patients groups, which seem to be of an immunological nature. This could be a factor, amongst others, for the better overall survival of the NPM1mut patient group. Furthermore we described new potential targets structures on CD34+CD38- cells for NPM1mut patient’s treatment. Disclosures: No relevant conflicts of interest to declare.

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