Nature子刊：白血病干细胞导致疾病复发
急性骨髓性白血病治疗后容易复发，日本研究人员发表最新研究报告说，其原因是白血病干细胞分裂缓慢，躲过了抗癌药物的攻击。
日本理化研究所石川文彦等人在10月22日的美国《自然—生物工艺学》杂志网络版上发表研究报告指出，他们向失去免疫能力的实验鼠注射采自人类白血病患者骨髓的白血病细胞，结果发现其中部分细胞虽然原本数量极少，却能大量增殖，引发白血病。
研究人员给上述发病的实验鼠注射抗癌药物，后来增殖产生的白血病细胞多数死亡，而最早注射入实验鼠体内的细胞却有70％到80％存活了下来。研究人员重新提取这些生存下来的细胞，注射入其他实验鼠体内，实验鼠随后也出现了白血病症状。
进一步研究显示，白血病干细胞的分裂速度较普通癌细胞缓慢，而抗癌药物一般针对增殖速度快的细胞，于是白血病干细胞恰好能躲过抗癌药物的攻击。另外，白血病干细胞集中存在于骨髓中抗癌药物难以达到的区域，这使得它们更难被消灭。（新华网）
原始出处:
Nature Biotechnology
Published online: 21 October 2007 | doi:10.1038/nbt1350
Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region
Fumihiko Ishikawa1,3, Shuro Yoshida1,3, Yoriko Saito1,5, Atsushi Hijikata2, Hiroshi Kitamura2, Satoshi Tanaka6, Ryu Nakamura7, Toru Tanaka7, Hiroko Tomiyama6, Noriyuki Saito3, Mitsuhiro Fukata3, Toshihiro Miyamoto4, Bonnie Lyons8, Koichi Ohshima9, Naoyuki Uchida10, Shuichi Taniguchi10, Osamu Ohara2,11, Koichi Akashi4,12, Mine Harada3 & Leonard D Shultz8
Acute myelogenous leukemia (AML) is the most common adult leukemia, characterized by the clonal expansion of immature myeloblasts initiating from rare leukemic stem (LS) cells1, 2, 3. To understand the functional properties of human LS cells, we developed a primary human AML xenotransplantation model using newborn nonobese diabetic/severe combined immunodeficient/interleukin (NOD/SCID/IL)2r
null mice carrying a complete null mutation of the cytokine c upon the SCID background4. Using this model, we demonstrated that LS cells exclusively recapitulate AML and retain self-renewal capacity in vivo. They home to and engraft within the osteoblast-rich area of the bone marrow, where AML cells are protected from chemotherapy-induced apoptosis. Quiescence of human LS cells may be a mechanism underlying resistance to cell cycle–dependent cytotoxic therapy. Global transcriptional profiling identified LS cell–specific transcripts that are stable through serial transplantation. These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells.
- Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho Tsurumi-ku, Yokohama 230-0045 Japan.
- Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho Tsurumi-ku, Yokohama 230-0045 Japan.
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582 Japan.
- Center for Cellular and Molecular Medicine, Kyushu University Hospital, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582 Japan.
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
- Nippon Becton Dickinson Company, 4-15-1 Akasaka Minato-ku, Tokyo 107-0052 Japan.
- Carl Zeiss, 22 Honshio-cho, Shinjuku-ku, Tokyo 160-0003 Japan.
- The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
- First Department of Pathology, Kurume University School of Medicine, 67 Asahi-cho, Kurume 830-0011 Japan.
- Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo 105-8470 Japan.
- Department of Human Genome Technology, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu 290-0818 Japan.
- Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Correspondence to: Fumihiko Ishikawa1,3 e-mail: f_ishika@rcai.riken.jp
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