Document Detail

The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia.
MedLine Citation:
PMID:  12406915     Owner:  NLM     Status:  MEDLINE    
In acute-type leukemia, no method for the prediction of relapse following allogeneic stem cell transplantation based on minimal residual disease (MRD) levels is established yet. In the present study, MRD in 72 cases of allogeneic transplantation for acute myeloid leukemia, acute lymphoid leukemia, and chronic myeloid leukemia (accelerated phase or blast crisis) was monitored frequently by quantitating the transcript of WT1 gene, a "panleukemic MRD marker," using reverse transcriptase-polymerase chain reaction. Based on the negativity of expression of chimeric genes, the background level of WT1 transcripts in bone marrow following allogeneic transplantation was significantly decreased compared with the level in healthy volunteers. The probability of relapse occurring within 40 days significantly increased step-by-step according to the increase in WT1 expression level (100% for 1.0 x 10(-2)-5.0 x 10(-2), 44.4% for 4.0 x 10(-3)-1.0 x 10(-2), 10.2% for 4.0 x 10(-4)-4.0 x 10(-3), and 0.8% for < 4.0 x 10(-4)) when WT1 level in K562 was defined as 1.0). WT1 levels in patients having relapse increased exponentially with a constant doubling time. The doubling time of the WT1 level in patients for whom the discontinuation of immunosuppressive agents or donor leukocyte infusion was effective was significantly longer than that for patients in whom it was not (P <.05). No patients with a short doubling time of WT1 transcripts (< 13 days) responded to these immunomodulation therapies. These findings strongly suggest that the WT1 assay is very useful for the prediction and management of relapse following allogeneic stem cell transplantation regardless of the presence of chimeric gene markers.
Hiroyasu Ogawa; Hiroya Tamaki; Kazuhiro Ikegame; Toshihiro Soma; Manabu Kawakami; Akihiro Tsuboi; Eui Ho Kim; Naoki Hosen; Masaki Murakami; Tatsuya Fujioka; Tomoki Masuda; Yuki Taniguchi; Sumiyuki Nishida; Yusuke Oji; Yoshihiro Oka; Haruo Sugiyama
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Publication Detail:
Type:  Evaluation Studies; Journal Article     Date:  2002-10-24
Journal Detail:
Title:  Blood     Volume:  101     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-13     Completed Date:  2003-04-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1698-704     Citation Subset:  AIM; IM    
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan.
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MeSH Terms
Acute Disease
Blast Crisis / blood,  genetics,  pathology,  therapy
Gene Expression Regulation, Leukemic*
Genes, Wilms Tumor*
K562 Cells / metabolism
Leukemia / blood,  genetics,  pathology,  therapy*
Leukemia, Myeloid, Accelerated Phase / blood,  genetics,  pathology,  therapy
Neoplasm Proteins / biosynthesis,  genetics*
Neoplasm, Residual / diagnosis
Peripheral Blood Stem Cell Transplantation*
Predictive Value of Tests
RNA, Messenger / biosynthesis*
RNA, Neoplasm / biosynthesis*
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Transplantation, Homologous
Treatment Outcome
WT1 Proteins / biosynthesis
Reg. No./Substance:
0/Neoplasm Proteins; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/WT1 Proteins
Comment In:
Blood. 2003 Jul 15;102(2):773-4; author reply 774   [PMID:  12835231 ]

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