TY - JOUR
T1 - BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia
AU - Bhattacharyya, Joyeeta
AU - Mihara, Keichiro
AU - Yasunaga, Shin'ichiro
AU - Tanaka, Hideo
AU - Hoshi, Masaharu
AU - Takihara, Yoshihiro
AU - Kimura, Akiro
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1007/s00277-008-0603-8
DO - 10.1007/s00277-008-0603-8
M3 - Article
C2 - 18781299
AN - SCOPUS:60749115380
SN - 0939-5555
VL - 88
SP - 333
EP - 340
JO - Annals of Hematology
JF - Annals of Hematology
IS - 4
ER -