title: Elevated expression of the AF1q gene, an MLL fusion partner, is an independent adverse prognostic factor in pediatric acute myeloid leukemia.
abstract: The AF1q gene, a mixed-lineage leukemia fusion partner, is highly expressed in hematopoietic progenitor cells but has low expression in differentiated cells. We determined the expression of the AF1q gene by reverse transcriptase-polymerase chain reaction in 64 pediatric acute myeloid leukemia (AML) patients treated on Children's Cancer Group clinical trial CCG-2891 and correlated its expression level to clinical characteristics and outcome. AF1q expression in patients varied from 0- to 154-fold compared with normal marrow, and increasing expression level was associated with worsening survival, with a hazard ratio of 1.02 per fold increase in AF1q expression (P = .032). We divided patients into tertile groups based on AF1q expression level. Patients with high AF1q expression (top tertile) had a higher predominance of French-American-British M1 compared to patients with lower 2 tertiles of AF1q expression (43% vs 9%, P = .003). High AF1q expression was associated with poor survival in univariate and multivariate models. Overall survival at 8 years for patients with the high AF1q expression was 19% versus 50% in patients with low AF1q expression, (P = .01). AF1q expression may correlate with clinical outcome in pediatric AML, although it is not clear if AF1q is simply a marker of a more primitive phenotype or contributes directly to leukemogenesis.
authors.affiliation: Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington School of Medicine, Seattle, USA. wwt3@case.edu.
authors.forename: William
authors.initials: W
authors.lastname: Tse
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: William G
authors.initials: WG
authors.lastname: Woods
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
mesh_terms: D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor; D001798:Blood Proteins / Q000235:genetics*; D001853:Bone Marrow / Q000502:physiology; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes / Q000235:genetics*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C091736:MLLT11 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase