title: The prognostic significance of IRF8 transcripts in adult patients with acute myeloid leukemia.
abstract: Interferon regulatory factor 8 (IRF8) is a transcription factor that plays a critical role in normal hematopoiesis, such that disruption of IRF8 activity promotes leukemogenesis. We and others have identified aberrant expression of IRF8 transcripts, including novel splice variants, in acute myeloid leukemia (AML), but studies have not investigated the prognostic significance of these transcripts. Therefore, we developed and optimized quantitative expression assays for both, the wild type, or the reference sequence (WT-IRF8) and novel splice variants (SV-IRF8). These assays were used to quantify IRF8 transcript levels in 194 adult patients with AML, and multivariate analyses investigated the prognostic significance of these expression levels. After adjusting for known prognostic factors, expression levels of WT- or SV-IRF8 transcripts were not significantly associated with complete responses or overall survival. However, increased expression of WT-IRF8 was associated with decreased relapse-free survival (RFS) in both univariate (P = 0.010) and multivariate (P = 0.019) analyses. Similarly, increased expression of SV-IRF8 was associated with a decreased RFS (univariate, P = 0.026 and multivariate, P = 0.021). These studies show for the first time that WT-IRF8 and SV-IRF8 are independent adverse prognostic factors for patients with AML. Additional studies are planned to examine the prognostic significance of IRF8 transcripts in other populations of AML patients.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Era L
authors: EL
authors: Pogosova-Agadjanyan
authors: Kenneth J
authors: KJ
authors: Kopecky
authors: Fabiana
authors: F
authors: Ostronoff
authors: Frederick R
authors: FR
authors: Appelbaum
authors: John
authors: J
authors: Godwin
authors: Hana
authors: H
authors: Lee
authors: Alan F
authors: AF
authors: List
authors: Jennifer J
authors: JJ
authors: May
authors: Vivian G
authors: VG
authors: Oehler
authors: Steve
authors: S
authors: Petersdorf
authors: Galina L
authors: GL
authors: Pogosov
authors: Jerald P
authors: JP
authors: Radich
authors: Cheryl L
authors: CL
authors: Willman
authors: Soheil
authors: S
authors: Meshinchi
authors: Derek L
authors: DL
authors: Stirewalt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099185:Interferon Regulatory Factor-8
chemical_list: D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D012333:RNA, Messenger; D000099185:Interferon Regulatory Factor-8
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