日本科学家发现25种可致白血病复发分子

scienese

--可据此开发出仅以白血病干细胞为标靶的新型药物
& `' G+ M. o/ l/ j$ J4 U     日本理化学研究所公布，该研究所免疫过敏科学综合研究中心的石川文彦和小原收等人组成的联合研究小组，发现了25种存在于白血病的干细胞中、可引起白血病复发的主要原因分子。根据这一发现，科学家可开发出保护正常血液干细胞、仅以白血病干细胞为标靶的新型药物，为从肝细胞着手根治白血病提供了根据。该研究成果发表在2月3日美国《科学—转化医学》（Science Translational Medicine）杂志的网络版上。% x% V* f7 a! j, I# F6 K( @# o3 s

) I% {' j1 Z' s急性骨髓性白血病是多发于成人的一种恶性血癌。迄今为止虽已开发出各种抗癌药物，能得到白血病细胞减少或症状改善的效果。但患者的病症会反复发作直至死亡，这仍是白血病治疗的最大难关。
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研究小组在之前的研究中发现，白血病复发的原因是白血病干细胞存在于骨髓中的特别场所，因而对抗癌药物具有抵抗性。
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2 [4 ]: q; C, e3 r研究小组为了解白血病干细胞的特征，对从白血病患者体内得到的白血病干细胞遗传基因，和能够正常制造免疫、血液细胞的正常造血干细胞进行了比较，发现了25种存在于白血病干细胞中的分子。这些分子包括白血病干细胞的细胞表面分子，制造白血病细胞时细胞增殖、生存所必需的激酶等酵素、以及与核中干细胞肿瘤有关的DNA特殊结合蛋白质等。这些分子可在白血病干细胞中发现，在维持正常血液、免疫的血液干细胞中却没有发现。
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研究小组用处于白血病状态的小鼠进行骨髓内病态成像处理，发现这些分子也存在于白血病干细胞的特殊场所。这就可杀死白血病干细胞、保护正常免疫，同时向实现根治急性骨髓性白血病又进了一步。
9 m/ V, F. Q9 H' O  P/ s  \) H作者：陈超 来源：科技日报 发布时间：2010-2-12 14:29:19
, d0 h1 U1 h: x" s& E3 IIdentification of Therapeutic Targets for Quiescent, Chemotherapy-Resistant Human Leukemia Stem CellsYoriko Saito1,*, Hiroshi Kitamura2,*, Atsushi Hijikata2, Mariko Tomizawa-Murasawa1, Satoshi Tanaka3, Shinsuke Takagi1, Naoyuki Uchida4, Nahoko Suzuki1, Akiko Sone1, Yuho Najima1, Hidetoshi Ozawa1, Atsushi Wake4, Shuichi Taniguchi4, Leonard D. Shultz5, Osamu Ohara2 and Fumihiko Ishikawa1,†  + u. t* {& x+ ^: b
1Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, Yokohama, 230-0045 Japan. 2 _( D. \$ t! W! W
2Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Yokohama, 230-0045 Japan. ' t- E$ ]; @7 e/ K8 Z% U8 T* u4 g
3Nippon Becton Dickinson Company, Tokyo, 107-0052 Japan. / {3 ?6 ?6 a/ E" q
4Department of Hematology, Toranomon Hospital, Tokyo, 105-8470 Japan.
+ q$ T# Z- b& [9 R5The Jackson Laboratory, Bar Harbor, ME 04609, USA.
- `5 Z% F5 \% D1 I6 D†To whom correspondence should be addressed. E-mail: f_ishika@rcai.riken.jp
& m5 f& f# ^' [  J* qSci Transl Med 3 February 2010
5 T: V# O% Z. D; AAbstract
% [# ]  @2 l* _% H4 KHuman acute myeloid leukemia (AML) originates from rare leukemia stem cells (LSCs). Because these chemotherapy-resistant LSCs are thought to underlie disease relapse, effective therapeutic strategies specifically targeting these cells may be beneficial. Here, we report identification of a primary human LSC gene signature and functional characterization of human LSC-specific molecules in vivo in a mouse xenotransplantation model. In 32 of 61 (53%) patients with AML, either CD32 or CD25 or both were highly expressed in LSCs. CD32- or CD25-positive LSCs could initiate AML and were cell cycle–quiescent and chemotherapy-resistant in vivo. Normal human hematopoietic stem cells depleted of CD32- and CD25-positive cells maintained long-term multilineage hematopoietic reconstitution capacity in vivo, indicating the potential safety of treatments targeting these molecules. In addition to CD32 and CD25, quiescent LSCs within the bone marrow niche also expressed the transcription factor WT1 and the kinase HCK. These molecules are also promising targets for LSC-specific therapy.