title: FLT3 expression and IL10 promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1.
abstract: We investigated the correlation between FLT3 expression and IL10 gene promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1 and their clinical significance. FLT3 mRNA expression was measured by real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) on bone marrow (BM) leukemic cells. IL10 gene promoter polymorphisms including rs1800896 (G-1082A), rs1800871 (C-819T), and rs1800872 (C-592T) were genotyped by direct sequencing. Among 45 enrolled patients, 32 (71.1 %) exhibited FLT3 overexpression, whose FLT3 mRNA level was higher than normal cut-off value (0.02). The IHC results also consisted with FLT3 mRNA expression data achieved by qPCR. The FLT3 mRNA level was significantly different among 3 IHC staining groups (P < 0.0001); 0.031 ± 0.041, 0.106 ± 0.097 and 0.588 ± 0.573 in IHC negative, intermediate and positive group, respectively. Interestingly, the FLT3 expression level was correlated with the percentage of BM CD34 positive cells (R = 0.360, P = 0.016). The elevated FLT3 expression at initial BM were decreased after remission and maintained lower than the cut-off level. FLT3 expression was not dependent on IL10 gene promoter polymorphisms. FLT3 overexpression itself did not demonstrate significant effects on overall survival (OS). However, it is notable that IL10 rs1800896 GA genotype tended to have a lower estimated mean OS (20.1 months) compared to GG genotype (54.6 months), but the statistical significance was not derived because of limited number of patients in this study (P = 0.072). Further studies including more type of leukemia and patients may be helpful to understand the relations between cytokine genotype and FLT3 expression and their prognostic impact.
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Jung Rok
authors.initials: JR
authors.lastname: Kim
authors.forename: Eunhee
authors.initials: E
authors.lastname: Han
authors.forename: Joonhong
authors.initials: J
authors.lastname: Park
authors.forename: Jihyang
authors.initials: J
authors.lastname: Lim
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Kyungja
authors.initials: K
authors.lastname: Han
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D053583:Interleukin-1beta; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D016753:Interleukin-10; D051941:fms-Like Tyrosine Kinase 3