title: New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts.
abstract: To evaluate the prognostic significance of quantitative PML-RARA, AML1-ETO, and CBFB-MYH11 fusion transcript expression, real-time polymerase chain reaction was used to analyze bone marrow samples of 349 such patients at diagnosis and 522 samples of 142 patients also during therapy (total analyses, n = 859; median number of follow-up samples, 4/patient; median duration of assessment, 12 months). Lower expression levels at diagnosis correlated with better overall and event-free survival in all 3 leukemia subtypes. By combining the median expression ratio after consolidation therapy and the 75th percentile of the expression ratio at diagnosis, a new score was established that separates a group with 100% EFS from a significantly worse group (P <.0001) in each of the 3 acute myeloid leukemia subgroups. Eight patients showed increasing levels of expression during follow-up and all had relapse. In conclusion, patients at high risk for treatment failure can be identified by high levels of fusion gene expression at diagnosis or less than 3 logs of tumor reduction during the first 3 to 4 months of therapy. By combining the transcription ratios at these 2 checkpoints, a new powerful prognostic score has been established.
authors.affiliation: Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. susanne.schnittger@med3.med.uni-muenchen.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Martin
authors.initials: M
authors.lastname: Weisser
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy*; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009693:Nucleic Acid Hybridization; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D012313:RNA