BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia.
BMI-1 plays a critical role in regulating the activity of hematopoietic stem and progenitor cells. Patients with chronic myeloid leukemia (CML) are at a risk of developing blastic crisis (BC) even after the emergence of imatinib mesylate. In this study, to determine the relevance of BMI-1 to BC, we investigated the expression of BMI-1 in CD34(+) cells at each of the chronic phase (CP), the accelerated phase (AP), and BC by flow cytometry. Interestingly, the level of BMI-1 expression was significantly higher in CP than in controls and was further increased during the course of the disease progression (control--5.66%; CP--36.93%; AP and BC--76.41%). Curiously, mRNA levels for BMI-1 were almost consistent during the disease progression from CP to BC (control--2.21; CP--9.77; AP and BC--9.70 (BMI-1/glyceraldehyde-3-phosphate dehydrogenase ratio)). Since we further found that overexpression of BCR-ABL in human embryonic kidney-293 cells enhanced BMI-1 expression and that BMI-1 expression was increased in K562 cells, derived from patients with BC, in the presence of proteasomal inhibitors, BMI-1 was presumed to be positively regulated by BCR-ABL and further by posttranscriptional modification in the course of the disease progression. We suggest the usefulness of BMI-1 expression in CD34(+) cells as a molecular marker for monitoring patients with CML.
Bhattacharyya
Joyeeta
J
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553 Hiroshima, Japan.
Mihara
Keichiro
K
Yasunaga
Shin'ichiro
S
Tanaka
Hideo
H
Hoshi
Masaharu
M
Takihara
Yoshihiro
Y
Kimura
Akiro
A
D018952:Antigens, CD34; D001752:Blast Crisis / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D016044:Fusion Proteins, bcr-abl / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics; D014158:Transcription, Genetic
D018952:Antigens, CD34; C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; D016044:Fusion Proteins, bcr-abl