The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia.
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.
Ogawa
Hiroyasu
H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan. ogachan@ceres.ocn.ne.jp
Tamaki
Hiroya
H
Ikegame
Kazuhiro
K
Soma
Toshihiro
T
Kawakami
Manabu
M
Tsuboi
Akihiro
A
Kim
Eui Ho
EH
Hosen
Naoki
N
Murakami
Masaki
M
Fujioka
Tatsuya
T
Masuda
Tomoki
T
Taniguchi
Yuki
Y
Nishida
Sumiyuki
S
Oji
Yusuke
Y
Oka
Yoshihiro
Y
Sugiyama
Haruo
H
D000208:Acute Disease; D001752:Blast Crisis / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015973:Gene Expression Regulation, Leukemic; D016162:Genes, Wilms Tumor; D006801:Humans; D020014:K562 Cells / Q000378:metabolism; D007938:Leukemia / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D018365:Neoplasm, Residual / Q000175:diagnosis; D036102:Peripheral Blood Stem Cell Transplantation; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012008:Recurrence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000096:biosynthesis
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025721:WT1 Proteins