Document Detail

Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels.
MedLine Citation:
PMID:  8822948     Owner:  NLM     Status:  MEDLINE    
Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT group and 3 in the BMT group who had achieved complete remission suffered clinical relapse. In 10 of these patients, WT1 expression that had returned to normal BM levels (< 10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradually or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patients, WT1 expression never returned to normal BM levels even after CR and the subsequent relapse was accompanied by a rapid increase in WT1 expression to levels higher than 10(-2) (10(-3) levels in PB). On the other hand, the remaining 35 patients (15 CHT and 20 BMT) maintained their CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression either gradually or rapidly decreased to normal BM levels, whereas in the other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(-3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quantitation of 168 paired BM and PB samples showed that PB samples were superior to BM samples for the detection of MRD. We conclude that monitoring of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinical relapse in the early stage for all leukemia patients regardless of the presence or absence of tumor-specific DNA markers.
K Inoue; H Ogawa; T Yamagami; T Soma; Y Tani; T Tatekawa; Y Oji; H Tamaki; T Kyo; H Dohy; A Hiraoka; T Masaoka; T Kishimoto; H Sugiyama
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Blood     Volume:  88     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-10-24     Completed Date:  1996-10-24     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2267-78     Citation Subset:  AIM; IM    
Department of Medicine III, Osaka University Medical School, Japan.
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MeSH Terms
Bone Marrow
Bone Marrow Transplantation
DNA-Binding Proteins / genetics*
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Leukemia / diagnosis,  genetics*
Neoplasm, Residual / diagnosis*
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Repressor Proteins / genetics
Transcription Factors / genetics*
WT1 Proteins
Wilms Tumor / genetics
Reg. No./Substance:
0/DNA-Binding Proteins; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Repressor Proteins; 0/Transcription Factors; 0/WT1 Proteins

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