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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3058-3063.
Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2003-12-4347.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Elevated expression of the AF1q gene, an MLL fusion partner, is an independent adverse prognostic factor in pediatric acute myeloid leukemia
William Tse,
Soheil Meshinchi,
Todd A. Alonzo,
Derek L. Stirewalt,
Robert B. Gerbing,
William G. Woods,
Frederick R. Appelbaum, and
Jerald P. Radich
From the Fred Hutchinson Cancer Research Center; the Department of Medicine and Department of Pediatrics, University of Washington School of Medicine, Seattle; Department of Medicine, University Hospital of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH; the Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Atlanta, GA; the Department of Biostatistics, University of Southern California Keck School of Medicine, Los Angeles; and the Children's Oncology Group, Arcadia, CA.
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.
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