Molecular mechanisms in the resistance of CML stem cells to tyrosine kinase inhibitors and novel targets for achieving a cure
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- TANAKA Hirokazu
- Department of Hematology and Rheumatology, Kinki University Faculty of Medicine
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- HIRASE Chikara
- Department of Hematology and Rheumatology, Kinki University Faculty of Medicine
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- MATSUMURA Itaru
- Department of Hematology and Rheumatology, Kinki University Faculty of Medicine
Bibliographic Information
- Other Title
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- CML幹細胞のチロシンキナーゼ阻害剤耐性機序と治癒を目指した新たな治療標的
- CML カンサイボウ ノ チロシンキナーゼ ソガイザイ タイセイ キジョ ト チユ オ メザシタ アラタ ナ チリョウ ヒョウテキ
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Abstract
Tyrosine kinase inhibitors (TKIs) have dramatically improved the clinical outcomes of patients with chronic myeloid leukemia (CML) in the chronic phase. However, even if these patients achieve and maintain marked molecular responses such as a complete molecular response (BCR-ABL/ABL≤0.032% by international scale), discontinuation of TKI treatment results in early molecular relapse in most cases. Although several factors such as the Sokal score and the duration of TKI treatment have been identified as being related to treatment-free remission (TFR), identification of more definite factors or clinical conditions that would enable us to select patients who can maintain TFR is required. Relapse after TKI discontinuation is considered to be attributable to CML stem cells surviving even in patients who maintain marked molecular responses. A number of in vitro experiments have shown that TKI by itself cannot kill CML stem cells. Also, CML stem cells are resistant to TKI in a manner dependent on self-renewal factors (Hh, Wnt/β-catenin), cell cycle regulators (PML), metabotropic factors (FOXO3, Alox5), and adhesion molecules (CXCR4). In addition, surface markers specific for CML stem cells such as IL-1RAP and CD26 have been identified. New therapeutic strategies targeting these molecules in combination with TKI hold promise of achieving a more effective strategy for curing CML.
Journal
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- Rinsho Ketsueki
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Rinsho Ketsueki 56 (2), 139-149, 2015
The Japanese Society of Hematology
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Details 詳細情報について
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- CRID
- 1390001205037349120
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- NII Article ID
- 130004920712
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- NII Book ID
- AN00252940
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- ISSN
- 18820824
- 04851439
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- NDL BIB ID
- 026217221
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- PubMed
- 25765793
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed