BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia

Joyeeta Bhattacharyya, Keichiro Mihara, Shin'ichiro Yasunaga, Hideo Tanaka, Masaharu Hoshi, Yoshihiro Takihara, Akiro Kimura

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalAnnals of Hematology
Volume88
Issue number4
DOIs
Publication statusPublished - 01-01-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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