title: Hox expression in AML identifies a distinct subset of patients with intermediate cytogenetics.
abstract: We previously reported that favorable and poor prognostic chromosomal rearrangements in acute myeloid leukemia (AML) were associated with distinct levels of HOX expression. We have now analyzed HOX expression in 50 independent adult AML patients (median age=62 years), together with FLT3 and FLT3-ligand mRNA levels, and FLT3 mutation determination. By cluster analysis, we could divide AMLs into cases with low, intermediate and high HOX expression. Cases with high expression were uniquely restricted to a subset of AMLs with intermediate cytogenetics (P=0.0174). This subset has significantly higher levels of FLT3 expression and appears to have an increase of FLT3 mutations (44%), while CEBPalpha mutations were infrequent (6%). FLT3 mRNA levels were correlated with the expression of multiple HOX genes, whereas FLT3 mutations were correlated with HOXB3. In some cases, FLT3 was expressed at levels equivalent to GAPDH in the absence of genomic amplification. We propose that high HOX expression may be characteristically associated with a distinct biologic subset of AML. The apparent global upregulation of HOX expression could be due to growth-factor signaling or, alternatively, these patterns may reflect a particular stage of differentiation of the leukemic cells.
authors.affiliation: CNRS UMR 6187, Université de Poitiers, 40 Av du Recteur Pineau, Poitiers, Cédex, France.
authors.forename: J
authors.initials: J
authors.lastname: Roche
authors.forename: C
authors.initials: C
authors.lastname: Zeng
authors.forename: A
authors.initials: A
authors.lastname: Barón
authors.forename: S
authors.initials: S
authors.lastname: Gadgil
authors.forename: R M
authors.initials: RM
authors.lastname: Gemmill
authors.forename: I
authors.initials: I
authors.lastname: Tigaud
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.forename: H A
authors.initials: HA
authors.lastname: Drabkin
mesh_terms: D000208:Acute Disease; D014408:Biomarkers, Tumor / Q000235:genetics*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D014408:Biomarkers, Tumor; D022763:CCAAT-Enhancer-Binding Protein-alpha; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3