title: Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia.
abstract: The WT1 gene is expressed in 73-100% of patients with acute myelogenous leukemia (AML) and is thought to play a role in maintaining the viability of leukemic cells. WT1 has been proposed as a marker for minimal residual disease in leukemia. We obtained serial blood or bone marrow samples from patients with de novo AML at diagnosis, during therapy, and up to 95 months after diagnosis and analyzed for WT1 gene expression by RT-PCR to determine whether gene expression was predictive of relapse. Forty-four patients had WT1-positive AML and achieved a complete remission (CR) following chemotherapy and 24 patients underwent unrelated donor (n = 4), sibling donor (n = 13) or autologous (n = 7) marrow transplantation. After achieving CR 62% of the patients became WT1-negative, while 38% remained WT1-positive. There was no difference in the disease-free survival (DFS) and survival from remission between WT1-positive and -negative patients (P > 0.1). Following BMT, 32% of the patients analyzed in CR within the first 100 days after transplantation were WT1 PCR positive. Detection of WT1 transcripts within 100 days following BMT did not affect DFS and overall survival (OS) after transplantation (P > 0.1). Ten of 11 patients who are in continuous CR following chemotherapy or BMT for more than 3 years were transiently WT1-positive during the observation period. Four of these patients displayed the WT1 transcript at the last examination. Thirteen of 39 patients were WT1 PCR negative within 4 months before clinical onset of relapse and eight patients were WT1 PCR negative at time of relapse. These data indicate that: (1) achievement of WT1 negativity is not associated with longer DFS, survival from remission, or OS after transplantation; (2) not all patients who relapse become WT1 positive again; (3) long-term remitters frequently display the WT1 transcript. Thus, we conclude that the monitoring of WT1 gene expression by qualitative RT-PCR during treatment and CR is of very limited value.
authors.affiliation: First Department of Medicine, University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Gaiger
authors.forename: D
authors.initials: D
authors.lastname: Schmid
authors.forename: G
authors.initials: G
authors.lastname: Heinze
authors.forename: B
authors.initials: B
authors.lastname: Linnerth
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.forename: P
authors.initials: P
authors.lastname: Kalhs
authors.forename: K
authors.initials: K
authors.lastname: Tisljar
authors.forename: S
authors.initials: S
authors.lastname: Priglinger
authors.forename: K
authors.initials: K
authors.lastname: Laczika
authors.forename: M
authors.initials: M
authors.lastname: Mitterbauer
authors.forename: M
authors.initials: M
authors.lastname: Novak
authors.forename: G
authors.initials: G
authors.lastname: Mitterbauer
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: U
authors.initials: U
authors.lastname: Jäger
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D015870:Gene Expression; D016162:Genes, Wilms Tumor; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000032:analysis*; D025721:WT1 Proteins
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D016044:Fusion Proteins, bcr-abl