Expression of Wilms' tumor gene 1 at different stages of acute myeloid leukemia and analysis of its major splice variants.
WT1 is a transcription factor involved in differentiation and proliferation of acute myeloid leukemia (AML) blasts and is expressed in 90% of cases, as determined by nested reverse transcription polymerase chain reaction (RT-PCR). It is proposed to be a key molecule in leukemia promotion. To assess the relevance of WT1 expression, we analyzed blood and bone marrow samples from 58 AML patients (37 at diagnosis, 8 in hematological remission, and 13 at relapse) for the level of WT1 expression, using quantitative real-time RT-PCR. In addition, 21 randomly chosen samples were also analyzed for the quantitative expression of the main WT1 splice variants. As expected, samples from patients at the time of diagnosis or relapse showed significantly higher WT1 expression compared to samples from patients in remission or control samples. No striking difference in expression levels was found between various French-American-British (FAB) subtypes. The level of WT1 expression observed in patients at the time of initial diagnosis was similarly high in patients at relapse. Expression of the four main isoforms (E5+/KTS+, E5-/KTS+, E5+/KTS-, and E5-/KTS-) was found in all samples with significantly higher expression levels of the E5+ variants. Together, these findings support the potential of WT1 as a target for novel treatment approaches in AML.
Siehl
Jan M
JM
Med. Klinik III (Hematology, Oncology and Transfusion Medicine), Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. janmichael.siehl@charite.de
Reinwald
Mark
M
Heufelder
Karin
K
Menssen
Hans D
HD
Keilholz
Ulrich
U
Thiel
Eckhard
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D016503:Drug Delivery Systems; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D012334:RNA, Neoplasm; D025721:WT1 Proteins