WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients - results from a single-centre study.
Following induction chemotherapy for acute myeloid leukaemia (AML), sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse and allow intervention at a more favourable stage than at overt relapse. We have determined the expression levels of the Wilms' tumour gene (WT1) by real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood and bone marrow in 133 newly diagnosed AML patients and compared them with those in healthy volunteers. At diagnosis, the WT1 level exceeded normal expression in 118 of 133 (89%) patients, and was high enough to allow for detection of a WT1 decrease of least 1000-fold in 98 of 133 (74%) patients following induction therapy. Concomitant monitoring of fusion transcripts (PML-RARalpha, AML1-ETO, MLL-MLL, CBFbeta-MYH11, or DEK-CAN) in 38 patients identified different relationships between WT1 and fusion transcript levels, the AML1-ETO group showing remarkably low levels of WT1 compared with fusion transcript. In 32 patients analysed longitudinally there was close concordance between relapse and increased WT1 levels. Parallel longitudinal monitoring of WT1 and fusion transcript showed close correlation in 18 of 18 patients. We conclude that WT1 expression by RQ-PCR may be employed as a tool to detect MRD in the majority of fusion transcript-negative AML patients.
Østergaard
Mette
M
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Olesen
Lene Hyldahl
LH
Hasle
Henrik
H
Kjeldsen
Eigil
E
Hokland
Peter
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015870:Gene Expression; D016162:Genes, Wilms Tumor / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D018365:Neoplasm, Residual; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055502:Secondary Prevention; D012680:Sensitivity and Specificity; D025721:WT1 Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D025721:WT1 Proteins