title: Reduction in WT1 gene expression during early treatment predicts the outcome in patients with acute myeloid leukemia.
abstract: Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (β-actin and ABL1, P<0.001). WT1 mRNA level at diagnosis was of no prognostic relevance (P>0.05). A≥1-log reduction in WT1 expression in bone marrow samples taken <1 month after diagnosis significantly correlated with an improved overall survival (P=0.004) and freedom from relapse (P=0.010) when β-actin was used as control gene. Furthermore, a reduction in WT1 expression by ≥2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P=0.004) and freedom from relapse (P=0.012). This result was achieved when normalizing against both β-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.
authors.affiliation: Department of Medical Biosciences, Umeå University, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Andersson
authors.forename: Xingru
authors.initials: X
authors.lastname: Li
authors.forename: Fryderyk
authors.initials: F
authors.lastname: Lorenz
authors.forename: Irina
authors.initials: I
authors.lastname: Golovleva
authors.forename: Anders
authors.initials: A
authors.lastname: Wahlin
authors.forename: Aihong
authors.initials: A
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D020732:Cytogenetic Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016879:Salvage Therapy; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D025721:WT1 Proteins