演題詳細

一般口演 / Oral Session

【E】一般口演 9 (Oral Session 9) :CML:Basic Research 1

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第7会場 / Room No.7 (ロイトン札幌 2F リージェント)
座長・司会
木村 晋也 (Shinya Kimura):1
1:Blood and Lung and Tumor Institute, Saga University, Japan
 
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Initial occupancy of leukemic stem cell correlates with prognostic factor in CML patients

演題番号 : OS-1-45

宮脇 恒太 (Kohta Miyawaki):1、岩崎 浩己 (Hiromi Iwasaki):2、赤司 浩一 (Koichi Akashi):1

1:Dept of Medicine and Biosystemic Science, Kyushu University、2:Center for Cellular and Molecular Medicine, Kyushu University Hospital

 

Background: Chronic myeloid leukemia (CML) stem cells are less sensitive to tyrosine kinase inhibitors (TKIs) compared to downstream progenitors. It might be possible that the initial leukemic stem cell burden affect the prognosis of chronic phase (CML-CP) patients, but this possibility has not been verified. The purpose of present study is to explore the clinical impact of the involvement of BCR-ABL positive clone in stem cell fraction at diagnosis.
Methods: CD34+ stem/progenitor cells; HSC, CMP, GMP and MEP fractions were isolated from bone marrow aspirate of 9 newly diagnosed CML-CP patients and subsequently analyzed the frequency of BCR-ABL positive clone by FISH analysis.
Results: Among myeloid progenitors, CMP and MEP populations robustly expanded and were composed almost entirely of BCR-ABL positive clone in all patients (FISH positive rate, 95.1±7.4% and 96.0±5.5%, respectively), while surprisingly GMP fraction was less involved in leukemia (56.3±37%). Importantly, HSC fraction was suppressed in CML patients compared to healthy volunteers, and the frequencies of BCR-ABL positive clone in HSC fraction (46.1±40.5%) were always less than those in CMP and MEP, suggesting that CML stem cell is less addictive to growth signaling of BCR-ABL compared to myeloid progenitors. Furthermore the leukemic stem cell occupancy fabulously correlated with prognostic scores such as Sokal, Hasford, and EUTOS.
Conclusion: The risk of disease progression and/or TKI sensitivity in CML-CP patients might be prospectively classified by the leukemic stem cell occupancy.

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