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4646 Background Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal disorders characterized by clinical and prognostic heterogeneity, mainly explained by different genetic abnormalities among other factors. The role of some key genes involved in disease pathogenesis in both entities remain unclear. Methods and patients Study objective was to analyse differences in gene expression related to angiogenesis, metabolism and cell proliferation, self-renewal and pluripotency in patients (pts) with MDS and AML. Thirty-three bone marrow (BM) samples at diagnosis were analysed and distributed in 4 different groups: control group (n=8), low-risk MDS (LR-MDS:<10% BM blasts; n=15), high-risk MDS (HR-MDS:>10% BM blasts; n=4) and AML (n=6). Total RNA was isolated from BM samples. Genes analysed were: vascular endothelial growth factor (VEGF) for angiogenesis, MYC, macrophage migration inhibitory factor (MIF) and glycogen synthase (GYS) for metabolism and cell-proliferation and Oct4 as transcription factor required to maintain an undifferentiated state for self-renewal and pluripotency. Gene expression was quantified by qRT-PCR in triplicate using ß-actin gene as control. SPSS software (v.16) and Mann-Whitney U-test were applied for statistical analysis (P value ≤.05 was considered significant in all cases). Results After analysis, only mRNA levels of VEGF and MYC showed significant difference between LR-MDS and the control group. However, higher expression of all genes were observed in HR-MDS vs LR-MDS (p≤.05) as shown in table 1. When compared HR-MDS to AML, no difference was observed in VEGF, MYC, MIF and GYS, but significant difference was noticed in mRNA expression of Oct4 in AML samples (p=.032) vs HR-MDS. Globally, gene expression in MDS (pts with LR and HR-MDS) was significant lower than in AML pts in all genes studied as expected. Conclusions Increased expression of VEGF, cMYC, MIF, GYS and OCT4 in HR-MDS vs LR-MDS and in AML vs MDS (global) suggests that these factors may play a relevant role in pathogenesis of both entities. These results point towards a different biological behaviour in less proliferative disease respect advanced stages and AML in different cellular pathways involved in disease progression. They might also justify clinical heterogeneity among patients with MDS and in patients with AML vs MDS as a sole group, and also being responsible for different response to treatment options. Analysis of protein expression is ongoing. Disclosures: No relevant conflicts of interest to declare.

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2530 Macrophage migration inhibitory factor (MIF) is a key mediator of the innate immune system by promoting pro-inflammatory functions, being involved in the pathogenesis of the sepsis, in inflammatory and autoimmune diseases, growth and cell differentiation, and in carcinogenesis. The recessive CC gene variant in -173G/C in the promoter region causes higher levels of MIF and it has been associated with sepsis, gastric cancer, and autoimmune diseases. We aimed to see whether this genetic variant influenced the clinical outcome of acute myeloid leukemia (AML) patients. Population study consisted of 277 AML patients from the Spanish cooperative CETLAM group. Median age of the patients was 45 (range, 15–74). According to MRC classification, 11% were of good risk, 70% of intermediate risk, and 11% of poor risk. For 8% of the patients MRC cytogenetical data was not available. Multivariate analysis for outcome was performed including age, MRC classification and leukocyte count. Results showed that recessive CC gene variant was associated with worse outcome than the other two genotypes (GG+GC). Thus, this gene variant was associated with lower overall survival (OS): 0% vs 28%, p<0.001, OR=5.19, p=0.002; and disease free survival (DFS): 0% vs 31%, p=0.003, OR=7.35, p=0.007 (Figure 1). Considering only patients with intermediate MRC, this recessive CC gene variant also retained its impact for OS (0% vs 27%, p=0.001; OR=5.96, p=0.003) and for DFS (0% vs 31%, p=0.005, OR=6.82, p=0.01). We restricted the analysis to patients who underwent allo-SCT, and this variant retained the worst prognostic value for OS (0% vs 54%, p=0.014, OR=10.89, p=0.037) and for DFS (0% vs 41%, p=0.027, OR=9.09, p= 0.05). Because this variant is associated with high expression of MIF, we analyzed MIF mRNA expression in healthy donors, in low and high risk myelodisplastic syndrome (MDS) patients, and in AML patients. Results showed a progressive increase of MIF expression from healthy donors to AML, presenting AML patients 31 fold higher MIF expression than donors (p<0.001). Furthermore, we analyzed the clinical impact of this recessive CC variant in MIF gene in a Spanish multicentre study of 490 adult donor-patient pairs who underwent HLA identical sibling allo-SCT. All patients were diagnosed with hematological malignancies. Median age was 45 (range, 16–69), 33% were in advanced phase of disease, and 38% received a reduced intensity conditioning regimen. This recessive CC gene variant when present in the patient was associated with higher frequency of death by sepsis or infection (83% of patients with this variant died of sepsis vs 17%, p=0.005). When the analysis was restricted to acute leukemia and MDS patients (N=234), this recessive CC gene variant was associated with higher transplant related mortality (73% vs 29%, p=0.02). Finally, we analyzed IFNγ production in peripheral blood of 180 blood donors after stimulation with cytomegalovirus (CMV) and phytohemagluttinin (PHA). Results showed that this variant (CC) was associated with higher IFNγ production after CMV exposure (p=0.003) and higher IFNγ production after PHA exposure (p=0.007). In conclusion, these results indicate the adverse prognostic impact of recessive CC gene variant in AML patients.Figure 1:A: Probability of overall survival (OS) and B: Probability of disease free survival (DFS) in the all group of AML patients according to 173G/C gene variant in MIF. GG+GC: patients carrying homozygous dominant variant + patients carrying heterozygous gene variant. CC: patients carrying recessive gene variant. Values obtained at multivariate analysis (OR and p) are shown.Figure 1:. A: Probability of overall survival (OS) and B: Probability of disease free survival (DFS) in the all group of AML patients according to 173G/C gene variant in MIF. GG+GC: patients carrying homozygous dominant variant + patients carrying heterozygous gene variant. CC: patients carrying recessive gene variant. Values obtained at multivariate analysis (OR and p) are shown. Disclosures: No relevant conflicts of interest to declare.