TY - JOUR
T1 - The Prognostic Significance of IRF8 Transcripts in Adult Patients with Acute Myeloid Leukemia
AU - Pogosova-Agadjanyan, Era L.
AU - Kopecky, Kenneth J.
AU - Ostronoff, Fabiana
AU - Appelbaum, Frederick R.
AU - Godwin, John
AU - Lee, Hana
AU - List, Alan F.
AU - May, Jennifer J.
AU - Oehler, Vivian G.
AU - Petersdorf, Steve
AU - Pogosov, Galina L.
AU - Radich, Jerald P.
AU - Willman, Cheryl L.
AU - Meshinchi, Soheil
AU - Stirewalt, Derek L.
PY - 2013/8/14
Y1 - 2013/8/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84881529198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881529198&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0070812
DO - 10.1371/journal.pone.0070812
M3 - Article
C2 - 23967110
AN - SCOPUS:84881529198
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 8
M1 - e70812
ER -