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3990 Multidrug resistance is one of the major prognostic factors in acute myeloid leukemia (AML). Expression of p-glycoprotein (p-gp), a member of the ABC transporter family and encoded by the ABCB1 gene, is associated with failure to respond to chemotherapy. Control of MDR1 expression is multifactorial and to-date emphasis has been on the 5'-promoter region of the gene. Evidence is now accumulating regarding a role for the 3'-untranslated region (3' UTR) of genes in controlling expression. We therefore studied a single nucleotide polymorphism (SNP) in the 3'UTR of ABCB1 (rs3842) and determined its effect on p-gp expression. Samples were available on 450 AML patients who had been entered into the UK LRF AML14 and NCRN AML15 trials. The distribution of the rs3482 A/G SNP was determined using the SNaPshot method; 10% of samples had their genotype confirmed by sequencing. P-gp protein expression and function were analysed by flow cytometry of CD45-gated cells; expression using MRK-16 and function by assessing the modulation of R123 accumulation by PSC833. To determine the activity of the two polymorphic alleles the 3'UTR of ABCB1 was cloned into a modified pGL3 luciferase vector and the normalised luciferase activity was assessed for both the A and G allele. The distribution of the rs3482 SNP in our AML patient cohort was 71% AA, 27% AG and 1.5% GG. These results are comparable with the published prevalence of the SNP in European populations. Approximately 60% of AML patients do not express p-gp so we therefore focused upon the 40% of patients who expressed p-gp. We found that in the p-gp-expressing patients a higher p-gp protein and function was associated with patients with the wild–type homozygous AA genotype when compared to the GA+GG genotypes. Furthermore when the ABCB1 3'UTR was cloned downstream of the firefly luciferase gene and transfected into HL-60 cells the ‘A’ construct demonstrated significantly increased activity when compared to the G construct (normalized ratio (firefly luciferase/renilla luciferase): A 7.7, G 1.9; n=4, p<0.05). Outcome data was available on 414 of the intensively treated trial patients. Whilst the ABCB1 3'UTR polymorphism had no impact on overall survival or relapse risk there was a trend towards an increased relapse free survival in patients with the wildtype AA genotype (RFS AA 37%; AG+GG 28%, p=0.08). This may correspond to higher p-gp expression in immunocompetent cells post-remission. In conclusion this work demonstrates that the ABCB1 rs3482 3'UTR SNP is functionally significant with the A allele associated with higher activity and a concomitant increase in p-gp expression and function in p-gp expressing patient samples. Disclosures: No relevant conflicts of interest to declare.

Purpose: to assess the frequency of ABO and Rh blood groups among Saudi and non-Saudi healthy blood donors and to compare between them. Methods: A retrospective study was conducted; in Makkah City, Saudi Arabia. It included 15,365 participants of 44 nationalities who have attended the blood bank of King Abdul Aziz Hospital. The collected data were age, sex, nationality, ABO, and Rhesus blood groups.  Results: 46.8 % of the participants were O, 28.8 % A, 19.5 % B, and 4.9% AB. The nationalities with a higher frequency of blood group O were Saudi, Mauritanian, Yemeni, Thai, Malian, Sudanese, Jordanian, Indian, Moroccan, Somali, Malaysian, Indonesian, Myanmar, Nigerian, Pakistani, Bangladeshi, Algerian, Djibouti, Burkinabe, Eritrean, Ghanaian, Bahraini, Bosnian, Canadian, Gambian, Iraqi, and Sri Lankan. Those with a higher frequency of blood group A were Turkish, Palestinian, Syrian, Lebanese, Egyptian, Afghan, Chadian, French, Tunisian, Cameroonian, Ethiopian, and British.  Those with a higher frequency of B were Nigerien, American, Nepalese, and two nationalities with higher AB frequency Filipino and Chinese. 91.6 % of all populations were Rh-positive, and 8.4% were Rh-negative. The Saudi participants were like some nationalities and differed from others. Conclusion:  In Makkah city, the higher frequency of ABO blood group in Saudi and non -Saudi people is O followed by A, then B, and AB.  The Rh-positive is predominant, and 8.4% of the participants are negative. The ABO and Rh blood groups' identifications are essential for providing suitable blood storage for individuals in need.