Application of the microarray technology to the transcriptional analysis of muscle phenotypes in pigs.

The transcriptome refers to the collection of all transcripts present in a cell. Gene expression has a very dynamic nature; it acts as a bridge between epigenetic marks, DNA sequence and proteins and changes to accommodate the requirements of the cell at each given time. Recent technological advances have created new opportunities to study complex phenotypes from a global point of view. From an animal production perspective, muscle transcriptomics has been investigated in relation to muscle growth, carcass fattening and meat quality traits. In this review, we discuss the impact of nutritional, anatomical and genetic factors on muscle gene expression and meat quality of pigs assessed by microarray technologies. Altogether, several common themes have been revealed by the in-depth analysis of the current body of knowledge, for instance, the involvement of genes related to energy balance and substrate turnover in the oxidative/glycolytic phenotype of red/white muscle fibre types and in the storage of intramuscular fat. The review also covers recent advances in the discovery of expression QTL and regulatory RNAs in porcine breeds as well as technical developments in the field of deep-sequencing technologies that are expected to substantially increase our knowledge about the genetic architecture of meat quality and production traits.

DECR1 and ME1 genotypes are associated with lipid composition traits in Duroc pigs.

Variation at the porcine DECR1 and ME1 genes has been associated with meat quality traits and backfat thickness in Landrace pigs, respectively. However, it has not been investigated yet whether DECR1 and ME1 genotypes influence lipid composition. With this aim, we have genotyped two missense DECR1 substitutions (c.160G>C and c.437G>C) and one silent ME1 (c.576C>T) polymorphism in 361 Duroc barrows distributed in five half-sib families and phenotyped for serum lipid concentrations and intramuscular fat content and composition traits. At the whole-population level, relevant associations, that is, with a posterior probability of the allele substitution effect to be over or below zero (PPN0) > 0.90, were observed between DECR1 genotype and serum cholesterol (CHOL) (PPN0 = 0.932) and LDL concentrations (PPN0 = 0.945) at 190 days, as well as between ME1 genotype and longissimus dorsi saturated fatty acid content (PPN0 = 0.924). At the within-family level, we found relevant associations between DECR1 and ME1 genotypes and diverse lipid composition traits, but most of them were family-specific. Discrepancies in allele substitution effects estimated in half-sib families might be produced by many factors such as number of individuals, marker allele frequencies and informativeness in each family, unaccounted random genetic and environmental effects, epistasis and family-specific differences in the linkage phase or amount of linkage disequilibrium between causal and marker mutations. This lack of consistency across families, combined with the fact that the ME1 mutation is synonymous and that the two DECR1 polymorphisms are conservative, suggests that the associations found are not causative.

Genetics of serum and muscle lipids in pigs.

Pork meat is one of the most important sources of animal protein in the human diet. Its nutritional properties are partly determined by intramuscular fat content and composition, with existing general consensus about the detrimental effects of cholesterol and saturated fat on cardiovascular health in humans. Because of their physiological resemblance, pigs can be also used as a valuable animal model to study the genetics of human diseases such as atherosclerosis, obesity and dyslipidaemias. Heritability estimates and QTL maps of porcine muscle and serum lipid traits evidence that a considerable amount of genetic variance determining these phenotypes exists, but its molecular basis remains mostly unknown. The recent advent of high-throughput genotyping and sequencing technologies has revolutionised the field of animal genomics. With these powerful tools, finding needles in the genomic haystack has become increasingly feasible. However, these methodological advances should not be deemed as magic bullets. The goal of identifying the many polymorphisms that shape the variability of lipid phenotypes is so challenging that success can be achieved only under the scope of large international consortia.

Mutation detection and typing of polymorphic loci through double-strand conformation analysis.

Variations, such as nucleotide substitutions, deletions and insertions, within genes can affect the function of the gene product and in some cases be deleterious. Screening for known allelic variation is important for determining disease and gene associations. Techniques which target specific mutations such as restriction enzyme polymorphism and oligonucleotide probe or PCR primer reactivity are useful for the detection of specific mutations, but these techniques are not generally effective for the identification of new mutations. Approaches for measuring changes in DNA conformation have been developed, based on the principle that DNA fragments which differ in nucleotide composition exhibit different mobilities after separation by polyacrylamide gel electrophoresis (PAGE). Here we describe a conformation-based mutation detection system, double-strand conformation analysis (DSCA), which provides a simple means to detect genetic variants and to type complex polymorphic loci. We demonstrate the application of DSCA to detect genetic polymorphisms such as a single-nucleotide difference within DNA fragments of up to 979 base pairs in length. We present the application of DSCA in detecting four different mutations in the cystic fibrosis gene (CFTR) and 131 different alleles encoded by HLA class I genes.

Quantitative trait loci analysis of a Duroc commercial population highlights differences in the genetic determination of meat quality traits at two different muscles.

We performed a whole-genome scan with 110 informative microsatellites in a commercial Duroc population for which growth, fatness, carcass and meat quality phenotypes were available. Importantly, meat quality traits were recorded in two different muscles, that is, gluteus medius (GM) and longissimus thoracis et lumborum (LTL), to find out whether these traits are determined by muscle-specific genetic factors. At the whole-population level, three genome-wide QTL were identified for carcass weight (SSC7, 60 cM), meat redness (SSC13, 84 cM) and yellowness (SSC15, 108 cM). Within-family analyses allowed us to detect genome-wide significant QTL for muscle loin depth between the 3rd and 4th ribs (SSC15, 54 cM), backfat thickness (BFT) in vivo (SSC10, 58 cM), ham weight (SSC9, 69 cM), carcass weight (SSC7, 60 cM; SSC9, 68 cM), BFT on the last rib (SSC11, 48 cM) and GM redness (SSC8, 85 cM; SSC13, 84 cM). Interestingly, there was low positional concordance between meat quality QTL maps obtained for GM and LTL. As a matter of fact, the three genome-wide significant QTL for colour traits (SSC8, SSC13 and SSC15) that we detected in our study were all GM specific. This result suggests that QTL effects might be modulated to a certain extent by genetic and environmental factors linked to muscle function and anatomical location.

Integrating Y-chromosome, mitochondrial, and autosomal data to analyze the origin of pig breeds.

We have investigated the origin of swine breeds through the joint analysis of mitochondrial, microsatellite, and Y-chromosome polymorphisms in a sample of pigs and wild boars with a worldwide distribution. Genetic differentiation between pigs and wild boars was remarkably weak, likely as a consequence of a sustained gene flow between both populations. The analysis of nuclear markers evidenced the existence of a close genetic relationship between Near Eastern and European wild boars making it difficult to infer their relative contributions to the gene pool of modern European breeds. Moreover, we have shown that European and Far Eastern pig populations have contributed maternal and paternal lineages to the foundation of African and South American breeds. Although West African pigs from Nigeria and Benin exclusively harbored European alleles, Far Eastern and European genetic signatures of similar intensity were detected in swine breeds from Eastern Africa. This region seems to have been a major point of entry of livestock species in the African continent as a result of the Indian Ocean trade. Finally, South American creole breeds had essentially a European ancestry although Asian Y-chromosome and mitochondrial haplotypes were found in a few Nicaraguan pigs. The existence of Spanish and Portuguese commercial routes linking Asia with America might have favored the introduction of Far Eastern breeds into this continent.

Association between the polymorphism of the goat stearoyl-CoA desaturase 1 (SCD1) gene and milk fatty acid composition in Murciano-Granadina goats.

Genetic variability of the caprine stearoyl-CoA desaturase 1 (SCD1) gene has been investigated by sequencing a 4.7-kb cDNA in 6 goats from the Murciano-Granadina and Malagueña breeds. Sequence alignment revealed the existence of one synonymous polymorphism at exon 5 (c.732C>T) and one nucleotide substitution (c.*3504G>A) at exon 6 that encodes the 3' untranslated region (UTR). Moreover, the existence of a previously reported 3'UTR polymorphism involving a 3-bp indel (c.*1902_1904delTGT) was confirmed. Single nucleotide polymorphism and haplotype-based association analyses revealed suggestive associations between genetic variability of the SCD1 locus and lactose, stearic, polyunsaturated, and conjugated linoleic fatty acid contents. Associations with milk fatty acid composition might be explained by the global effects that SCD1 exerts on mammary gland lipid metabolism through the down-modulation of key transcription factors. Interestingly, the performance of an in silico analysis revealed that the c.*1902_1904delTGT polymorphism involves a considerable change in the secondary structure of the SCD1 mRNA. Gene reporter assays and quantitative PCR analysis would be needed to assess if this mutation has a causal effect on milk polyunsaturated and conjugated linoleic fatty acid levels by altering the amount of SCD1 transcripts in mammary epithelial cells.

[Clinical impact of HLA disparities in transplants from unrelated donors]. / Disparidad HLA y trasplante de donante no emparentado.

The search for an unrelated donor must be based on the HLA typing of the donor and the host. PCR techniques have facilitated high-resolution HLA typing, but they have also elicited questions about the real impact of the various disparities on the progress of the graft Thus, whereas a donor used to be accepted based on HLA-A and B Identity determined by serology and HLA-DRB1 through molecular biology techniques, now a donor is required to have a 70/70 Identity for loci HLA-A, B, C, DRB7, and DQB7. Furthermore, the real effect of the disparities in the sixth locus of the major histocompatibility complex-HLA-DPBT-is still in doubt. This study intends to conduct a literature review of the clinical impact of the various HLA disparities In transplants from unrelated donors.

Quasi-binomial zero-inflated regression model suitable for variables with bounded support.

In recent years, a variety of regression models, including zero-inflated and hurdle versions, have been proposed to explain the case of a dependent variable with respect to exogenous covariates. Apart from the classical Poisson, negative binomial and generalised Poisson distributions, many proposals have appeared in the statistical literature, perhaps in response to the new possibilities offered by advanced software that now enables researchers to implement numerous special functions in a relatively simple way. However, we believe that a significant research gap remains, since very little attention has been paid to the quasi-binomial distribution, which was first proposed over fifty years ago. We believe this distribution might constitute a valid alternative to existing regression models, in situations in which the variable has bounded support. Therefore, in this paper we present a zero-inflated regression model based on the quasi-binomial distribution, taking into account the moments and maximum likelihood estimators, and perform a score test to compare the zero-inflated quasi-binomial distribution with the zero-inflated binomial distribution, and the zero-inflated model with the homogeneous model (the model in which covariates are not considered). This analysis is illustrated with two data sets that are well known in the statistical literature and which contain a large number of zeros.

Polymorphism of the pig acetyl-coenzyme A carboxylase alpha gene is associated with fatty acid composition in a Duroc commercial line.

Acetyl-coenzyme A carboxylase alpha (ACACA) catalyses the first committed step in the biosynthesis of long-chain fatty acids (FA) by converting acetyl-CoA into malonyl-CoA. In pigs, the ACACA gene maps to a chromosome 12 QTL with important effects on FA composition. In the present study, we have sequenced the coding region of the pig ACACA gene in 15 pigs, identifying 21 polymorphic sites that were either synonymous or non-coding. Ten of these SNPs segregated in a Duroc commercial population (n = 350) for which lipid metabolism and meat and carcass quality trait records were available. Significant associations were found between two linked single nucleotide polymorphisms (c.4899G>A and c.5196T>C) and percentages of carcass lean, intramuscular fat, monounsaturated, saturated (myristic, palmitic and stearic) and polyunsaturated (linoleic) FAs in the longissimus thoracis et lumborum muscle, along with serum HDL-cholesterol concentration. The most important allele substitution effects were observed for the polyunsaturated/saturated FA ratio (13-21% of the phenotypic mean) as well as for the percentages of omega-6 and polyunsaturated FAs, especially linoleic acid (7-16% of the phenotypic mean). These results suggest the existence of a causal mutation, mapping to the chromosomal region containing the pig ACACA gene, with marked effects on FA composition of meat.

Nucleotide sequence and association analysis of pig apolipoprotein-B and LDL-receptor genes.

Three genes are the major determinants of heritable hypercholesterolemia diseases in humans: APOB, LDLR and LDLRAP1, which encode for proteins that physically interact to promote cholesterol uptake in the cell. We have carried out association analyses of these variants with serum cholesterol and triglycerides concentrations in a half-sib Duroc pig population. Given the structure of the population (six paternal half-sib families), we have used a statistical model that considers separately the allele transmission through dams (at population level) and through sires (within-families from heterozygous sire). Only polymorphisms showing a relevant substitution effect for both male- and female-transmitted alleles are likely to be causal mutations. Thus, although we have found statistical association between genotypes for LDLR and APOB polymorphisms and serum lipid levels (mean allele substitution effects ranging from 15 to 40% of the standard deviation of these traits), none of them seem to be the causal mutation but probably represent closely linked polymorphisms. We have shown here that these three genes also contribute to genetic variability in pigs, with the description of new polymorphisms in their coding regions. Moreover, we have demonstrated that variants on two of these three genes are segregating in a number of commercial breeds. Finally, we report here the coding region for the porcine LDLRAP1 gene and describe a polymorphism in the last exon of this gene.

A photoluminescence study of film structure in CdTe nanoparticle thin films.

The layer-by-layer deposition of thin films of CdTe nanoparticles and three different polyelectrolytes has been investigated. Photoluminescence spectra were used to monitor the energy transfer properties within the films. As the number of bilayers in a thin film was increased a decrease in the energy of the light emitted was observed. The wavelength change is a two-stage process. Deposition of the first one to two bi-layers of a thin film produced a sharp energy change (626 nm to 637 nm with the addition of a single bi-layer) whereas deposition of subsequent bi-layers produced a more gradual energy change (642 nm-646 nm with the addition of 5 bi-layers). A space-filling mechanism is suggested to account for these changes; smaller nanoparticles penetrate the earlier levels of a thin film and increase the inter-particle energy transfer opportunities within the layers.

Red shift for CdTe nanoparticle thin films and suspensions during heating.

The work that we have conducted shows that temperature affects the wavelength of light emitted from CdTe nanoparticle clusters that are in a suspension or deposited into thin films via a layer-by-layer process. Compared with the stock suspension, the films show an initial photoluminescent shift, of circa 6-8 nm to the red, when the particles are deposited. A shift of circa 6-8 nm is also seen when the suspensions are first heated to 85 degrees C from room temperature (20 degrees C) having been stored in a fridge at 5 degrees C. This shift is non-recoverable. With continual cycling from room temperature to 85 degrees C the suspensions show a slight tendency for the emission to move increasingly to the red; whereas the films show no such tendency. In both cases, the range in emission is ca 10 nm from the room temperature state to 80 degrees C. The intensity of the emission from the film drops abruptly (ca 50% reduction) after one cycle of heating; in the suspension there is an initial increase (ca 3-5% increase) in intensity before it decays. We see that the shift towards the red has been attributed to energy transfer or a rearrangement of the packing of the particles in the thin films. After conducting analysis of the films using scanning probe microscopy we have determined that a change in the morphology is responsible for the permanent shift in emission wavelength associated with prolonged heating. The influence of traps has not been ruled out, but the morphological change in the samples is very large and is likely to be the dominating mechanism affecting change for the red shift at room temperature.

Burkholderia tropica as a Potential Microalgal Growth-Promoting Bacterium in the Biosorption of Mercury from Aqueous Solutions.

The use of microalgal biomass is an interesting technology for the removal of heavy metals from aqueous solutions owing to its high metal-binding capacity, but the interactions with bacteria as a strategy for the removal of toxic metals have been poorly studied. The goal of the current research was to investigate the potential of Burkholderia tropica co-immobilized with Chlorella sp. in polyurethane discs for the biosorption of Hg(II) from aqueous solutions and to evaluate the influence of different Hg(II) concentrations (0.041, 1.0, and 10 mg/l) and their exposure to different contact times corresponding to intervals of 1, 2, 4, 8, 16, and 32 h. As expected, microalgal bacterial biomass adhered and grew to form a biofilm on the support. The biosorption data followed pseudo-second-order kinetics, and the adsorption equilibrium was well described by either Langmuir or Freundlich adsorption isotherm, reaching equilibrium from 1 h. In both bacterial and microalgal immobilization systems in the coimmobilization of Chlorella sp. and B. tropica to different concentrations of Hg(II), the kinetics of biosorption of Hg(II) was significantly higher before 60 min of contact time. The highest percentage of biosorption of Hg(II) achieved in the co-immobilization system was 95% at pH 6.4, at 3.6 g of biosorbent, 30 ± 1°C, and a mercury concentration of 1 mg/l before 60 min of contact time. This study showed that co-immobilization with B. tropica has synergistic effects on biosorption of Hg(II) ions and merits consideration in the design of future strategies for the removal of toxic metals.

New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas.

Human epithelial tumors need to accumulate multiple genetic alterations to form invasive carcinomas. These genetic alterations are related with growth factor receptors, cell signalling, the cell cycle and cell invasiveness. Importantly, cells need to avoid senescence and become immortalized for this process. Recently, five genes: RPS6KA6, HDAC4, KIAA0828, TCP1 and Tip60, which modulate p53-dependent function and avoid senescence were identified in a large-scale RNA interference screen. Twenty colon, 20 prostate and 20 lung carcinomas were studied to investigate whether these genes might be related with human tumors. RNA was extracted from both normal and tumor tissue from each patient. Real-time RT-PCR was performed using TaqMan probes corresponding to the RPS6KA6, HDAC4, KIAA0828, TCP1, Tip60 and p53 genes. In colon carcinomas, the RPS6KA6, HDAC4, KIAA0828 and Tip60 genes were downregulated in tumor tissue as compared with normal tissue (P < 0.001 for all genes). In lung carcinomas, HDAC4, KIAA0820 and Tip60 were downregulated (P < 0.01, P < 0.001 and P < 0.001 respectively). Whereas no significant differences were observed in prostate carcinomas, striking downregulation of the RPS6KA6 and KIAA0828 genes was observed in colon carcinomas and KIAA0828 in a subset of lung carcinomas. mRNA expression of these genes may control p53 function as well as the ras-MAPK pathway, methylation and transcriptional cellular programs. These results could unravel a novel set of regulatory suppressor genes involved in human colon and lung tumors.

Adenovirus-based transfer of wild-type p53 gene increases ovarian tumor radiosensitivity.

The p53 tumor suppressor gene product is known to be active in mediating radiation-induced G1-S cell cycle arrest and apoptosis in a number of normal cell lines. These functions are compromised by inactivation of p53, which promotes tumor progression. Because the p53 gene appears to play an important role in the cellular response to radiation, wild-type p53 gene replacement might be expected to increase the sensitivity of malignant cells with mutant p53 to the cytotoxic effects of ionizing radiation. This study demonstrates that adenovirus (AdV)-mediated transfer and expression of the wild-type p53 in malignant cells lacking the p53 gene results in an increase in cellular radiosensitivity in vitro and tumor radioresponsiveness in vivo. Cultures of the p53 double deletion mutant ovarian cell line SK-OV-3 were infected with nonreplicative adenoviral vectors containing either the wild-type p53 gene (AdVp53) or the luciferase gene (AdVluc). Cultures infected with AdVp53 efficiently expressed wild-type p53 protein and were more sensitive to radiation than uninfected cultures or cultures infected with AdVluc. The ability of AdVp53 to radiosensitize tumors in vivo was tested using SK-OV-3 tumors growing in the flanks of severe combined immune-deficient mice. Intratumoral injection with AdVp53, but not AdVluc, led to enhanced radioresponsiveness and 45% long-term tumor control. These studies demonstrate the ability of AdVp53 to effectively transfer and express p53 protein in established tumors with a resultant increase in radiation responsiveness.

Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene.

The management of human breast cancer frequently includes radiation therapy as an important intervention, and improvement in the clinical efficacy of radiation is desirable. Overexpression of the HER-2 growth factor receptor occurs in 25-30% of human breast cancers and correlates with poor clinical outcome, including earlier local relapse following conservative surgery accompanied by radiation therapy. In breast cancer cells with overexpression of HER-2 receptor, recombinant humanized monoclonal antibodies (rhuMAbs) to HER-2 receptors (rhuMAb HER-2) decrease cell proliferation in vitro and reduce tumor formation in nude mice. Therapy with rhuMAb HER-2 enhances tumor sensitivity to radiation at doses of 1-5 Gy, exceeding remission rates obtained with radiation alone. This benefit is specific to cells with HER-2 overexpression and does not occur in cells without overexpression. Treatment of cells with radiation (2-4 Gy) alone provokes a marked increase in unscheduled DNA synthesis, a measure of DNA repair, but HER-2-overexpressing cells treated with a combination of rhuMAb HER-2 and radiation demonstrate a decrease of unscheduled DNA synthesis to 25-44% of controls. Using an alternate test of DNA repair, i.e., radiation-damaged or undamaged reporter DNA, we introduced a cytomegalovirus-driven beta3-galactosidase into HER-2-overexpressing breast cancer cells that had been treated with rhuMAb HER-2 or control. At 24 h posttransfection, the extent of repair assayed by measuring reporter DNA expression was high after exposure to radiation alone but significantly lower in cells treated with combined radiation and rhuMAb HER-2 therapy. To further characterize effects of rhuMAb HER-2 and the combination of antibody and radiation on cell growth, analyses of cell cycle phase distribution were performed. Antibody reduces the fraction of HER-2-overexpressing breast cancer cells in S phase at 24 and 48 h. Radiation treatment is also known to promote cell cycle arrest, predominantly at G1, with low S-phase fraction at 24 and 48 h. In the presence of rhuMAb HER-2, radiation elicits a similar reduction in S phase at 24 h, but a significant reversal of this arrest appears to begin 48 h postradiation exposure. The level of S-phase fraction at 48 h is significantly greater than that found at 24 h with the combined antibody-radiation therapy, suggesting that early escape from cell cycle arrest in the presence of antireceptor antibody may not allow sufficient time for completion of DNA repair in HER-2-overexpressing cells. Because it is well known that failure of adequate p21WAF1 induction after DNA damage is associated with failure of cell cycle arrest, we also assessed the activity of this critical mediator of the cellular response to DNA damage. The results show induction of p21WAF1 transcripts and protein product at 6, 12, and 24 h after radiation treatment; however, increased levels of p21WAF1 transcript and protein are not sustained in HER-2-overexpressing cells exposed to radiation in the presence of rhuMAb HER-2. Although transcript and protein levels increase at 6-12 h, they are both diminished by 24 h. Levels of p21WAF1 transcript and protein at 24 h are significantly lower than in cells treated by radiation without antibody. A reduction in the basal level of p21WAF1 transcript also occurred after 12-24 h exposure to antibody alone. The effect of HER-2 antibody may be related to tyrosine phosphorylation of p21WAF1 protein. Tyrosine phosphorylation of p21WAF1 is increased after treatment with radiation alone, but phosphorylation is blocked by combined treatment with antireceptor antibody and radiation. This dysregulation of p21WAF1 in HER-2-overexpressing breast cells after treatment with rhuMAb HER-2 and radiation appears to be independent of p53 expression levels but does correlate with reduced levels of mdm2 protein. (ABSTRACT TRUNCATED)

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.