88-P: HIGH FREQUENCY OF THE +3010 G AND +3142 C ALLELES OF THE 3’ UNTRANSLATED REGION OF THE HLA-G GENE AND VARIABLE LEVELS OF SOLUBLE sHLA-G IN CHILDHOOD ACUTE MYELOID LEUKEMIA

Abstract

Polymorphisms at the 3’Untranslated region (UTR) of the HLA-G gene may influence the plasma sHLA-G. Although high levels of plasma sHLA-G have been associated with less favorable outcome in malignant hematological disorders, no information is available regarding sHLA-G in bone marrow aspirates. We evaluated the HLA-G 3’UTR allele, genotype and haplotype frequencies and bone marrow aspirate sHLA-G levels in patients exhibiting childhood acute myeloid leukemia. The HLA-G 3’UTR polymorphisms were studied in 109 children with acute myeloid leukemia followed-up at the IMIP Hospital in Recife, and 76 healthy children from the same Brazilian region. Leukemia cells were characterized by flow cytometry, and molecular biology for the detection of chromosomal translocation and gene mutations. The HLA-G polymorphism was detected by sequencing analysis and sHLA-G was detected by ELISA. Leukemia was classified in LMA-M5 (28%) and -M3 (23%) in most cases. Genetic alteration was identified in 55% of cases. Leukemia parameters of complete remission (56%), relapse (35%), second neoplasia (9%) and death (61%) illustrate the disease prognosis in this setting. The +3010 G-G ( p =0.007; OR=3.8) and +3142 C-C ( p = 0.003, OR=4.33) 3’UTR HLAG genotypes, and UTR-6 haplotype ( p = 0.019 and OR=4.63) were overrepresented in myeloid leukemia study group. Normal bone marrow of 12 children age 0 to 13 years showed average level of sHLA-G of 197 U/mL ± 23 U/mL, however, the. sHLA-G production in leukemic environmental was variable. From 40 pathological bone marrow analysed, 29 showed lower levels of sHLA-G, 7 presented high levels of sHLA-G and only 4 showed levels similar to the normal bone marrow control group. 3’UTR HLA-G alleles were associated with the development of childhood myeloid leukemia, however, the level of sHLA-G expression in leukemic environmental was highly variable in relation to the normal bone marrow.