Cell: 干细胞疗法预防白血病复发获进展 (转）

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Stem Cell Treatment to Prevent Leukemia Returning Is a Step Closer, Say Scientists
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译者：Docofsoul（丁香园学术观察员）
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# }1 C0 s2 U7 w& Q# x/ iScienceDaily (June 2, 2011)— Researchers at King's College London have identified a way of eliminating leukemic stem cells, which could lead to new treatments that may enable complete remission for leukemia patients. An early study in mice has shown that leukemic stem cells can be abolished by suppressing two proteins found in the body.
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- `" Z  `/ ?2 `; S- K4 I《每日科学》2011年6月2日报道——伦敦国王学院的研究者找到了一种清除白血病干细胞的新方法，由此可催生新的治疗手段，有望使白血病患者完全缓解。这项小鼠模型的早期研究表明：通过抑制体内发现的两种蛋白质可彻底摧毁白血病干细胞。) u  E  ^6 W2 f" L

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Stem cells. (Credit: Image courtesy of King's College London)6 e4 O  H6 q) {9 ^" e4 c! Y
干细胞（图片来源：伦敦国王学院）
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Leukemic stem cells sustain the disease and are likely to be responsible for relapse, so elimination of these cells is believed to be key for achieving complete remission. These encouraging findings highlight the two proteins as potential therapeutic targets to prevent the most aggressive forms of leukemia returning. The study, funded by Cancer Research UK and leukemia Lymphoma Research, is to be published in the journal Cell Stem Cell.0 d( F' ]7 [5 P" X' l+ \) z- R
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白血病干细胞是维持白血病的幕后推手，也是导致白血病复发的可能元凶，因此医学界相信消灭白血病干细胞是彻底缓解白血病的关键所在。本项研究之所以令人鼓舞，在于发现了两种有望成为治疗靶标的蛋白质，可籍此预防恶性白血病的复发。该研究由英国癌症研究协会与白血病与淋巴瘤研究协会提供资金，将发表于《Cell Stem Cell》（2010年该刊影响因子为23.5左右——译者）。! k" n  c* e- q6 ]$ O
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King's scientists looked at leukemic stem cells found in a type of leukemia that involves mutations of the MLL gene. This accounts for around 70 per cent of infant leukemias and 10 per cent of adult acute leukemias. The prognosis for MLL in children is not good -- only 50 per cent survive past two years after receiving standard treatment.
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' T/ w( e& ]' `( \( N7 |+ n本研究中科学家所关注的白血病干细胞发现于与MLL基因相关的一类血癌。这类血癌占幼儿白血病的70%、成人急性白血病的10%。儿童MLL预后差——接受标准治疗后超过两年的生存率只有50%。, \! x6 q1 H* J9 J  B0 F) g/ Y( E
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The protein Bmi1 was already known to play a key role in the survival and proliferation of various cancer stem cells. But this study has for the first time shown that, although the protein is needed for survival of various Acute Myeloid leukemia (AML) cells, in MLL leukemia the cancer stem cells actually survive independently of Bmi1. This shows that for these MLL patients, targeting Bmi1 alone would not have a major impact on eradicating leukemic stem cells, as was previously thought.
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  x0 D3 x5 N) r6 D) w( d, \已知Bmi1蛋白在各种肿瘤干细胞的生存与扩散中扮演着关键角色。但本研究则首次显示：虽然该蛋白为各种急性骨髓性白血病（AML）细胞的生存所需，但在MLL白血病中，该肿瘤干细胞的生存实际上并不依赖于Bmi1。这表明：对于MLL患者而言，仅仅以Bmi1为靶标来清除白血病干细胞可能徒劳无益；此前科学家们也的确想到了这一点。
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However, the team also found high levels of another protein called Hoxa9 in the MLL mice and human patients. Similar to Bmi1, a major role of this protein is to ensure leukemia cells divide and grow by allowing their escape from the inherent surveillance system, which will otherwise cause cell death. They found that in mice with MLL leukemic stem cells (that can proliferate without Bmi1), suppression of both Bmi1 and Hoxa9 completely abolishes the ability of MLL mutation to induce leukemia.* K0 s, _# R0 r

4 o7 k5 D& d1 k$ h# G不过，研究小组也在MLL小鼠与人类患者体内发现高水平的Hoxa9蛋白。与Bmi1相似，该蛋白的一个主要角色是让白血病细胞逃避先天性（免疫）监控系统以确保白血病细胞分化与生长，不然的话监控系统就会对这些细胞格杀勿论。研究者发现，体内存在MLL白血病干细胞（能够在没有Bmi1的情形下繁殖）的小鼠，如果对Bmi1与Hoxa9同时加以抑制，则MLL突变诱导白血病的能力就会被完全剥夺。
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These findings provide evidence for the different pathways involved in the development of different types of leukemic stem cells, and highlight the importance of targeting Bmi1 and Hoxa9 together to abolish MLL leukemic stem cells in particular.
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存在着这种观点：不同类型的白血病干细胞的发育与不同通道相关。本研究显然为此提供了证据；尤其是，本研究突出了同时针对Bmi1与Hoxa9以彻底清除MLL白血病干细胞的重要意义。6 I* B9 d7 P5 n) p- s/ y

; S2 B9 P0 e' L  {$ ZProfessor Eric So, Head of the leukemia and Stem Cell Biology group at King's, said: 'These findings take us a step forward in our understanding of how this devastating disease can return in patients after they have received the standard treatment.
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国王学院白血病与干细胞生物学组组长Eric So教授说：“这些发现使我们对白血病这种毁灭性疾病何以在病人接受标准治疗后又会复发的相关机制有了进一步的理解。- e) T+ Z$ r' W- i* i7 U, L* g

; J1 w, r4 E5 B) C7 d0 ['Now we know that leukemic stem cells in certain types of leukemia, such as MLL, can survive and proliferate independently of the Bmi1 protein, we need to consider more carefully the future of stem cell therapy to treat the disease. It's not as easy as people originally thought it might be.
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“现在明白了：某些特定类型的白血病（比如说MLL）中白血病干细胞能够无需Bmi1就能生存、增殖；我们需要更加谨慎地审视白血病干细胞疗法的未来，因为事情并非象人们原来设想的那样轻而易举。
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6 P9 K/ D- {  z1 |: A3 k3 s'But these findings provide us with vital information that will help us look at alternative ways of combating different forms of the disease, which will ultimately allow patients to achieve long-term complete remission.4 y+ ^! t4 `' d% n# g6 o
'What we need to do now is to find out exactly how Bmi1 and Hoxa9 proteins sustains the growth of cancer cells in order to develop an effective treatment to stop the disease returning.'
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& A) O8 n2 Y5 o“但是这些发现让我们掌握了至关重要的信息，将有助于我们寻找战胜不同类型白血病的可供选择的方法并最终让患者达到长期完全缓解。现在需要做的工作是找出Bmi1与Hoxa9蛋白维持癌细胞生长的具体机制，然后对症下药，开发阻断疾病复发的有效疗法。”
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& Q7 ~4 a4 e: S, q4 LProfessor Peter Johnson, Cancer Research UK's chief clinician, said: 'This study builds on previous Cancer Research UK-funded work trying to pinpoint the molecules responsible for driving the development of MLL-related leukemia stem cells.
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英国癌症研究院主任医师Peter Johnson教授说：“这项研究是此前英国癌症研究院所资助的、目的在于确认促使MLL相关白血病干细胞发育的分子的相关研究的发展。
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7 w" Z0 j  v, e! S$ ~0 {9 D6 z8 G'Cancer stem cells appear to be more resistant to radiotherapy and chemotherapy than the other leukemia cells, so understanding how they originate -- and how we can kill them -- will be a major step in being able to help even more people survive leukemia in future.'
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+ W& s* g) a7 Z$ m+ y“比起其它白血病细胞来，白血病干细胞对放射疗法与化学疗法更具抵抗性；因此，理解其发生发展机制并研究杀灭的相关方法将有助于更多的人们在未来遭受白血病攻击时生存下来，此中意义，不言自喻。”# n! U3 f1 k' g% `

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参考文献：- V. e6 M- W* Y! r; T
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Lan-Lan Smith, Jenny Yeung, Bernd B. Zeisig, Nikolay Popov, Ivo Huijbers, Josephine Barnes, Amanda J. Wilson, Erdogan Taskesen, Ruud Delwel, Jesús Gil et al. Functional Crosstalk between Bmi1 and MLL/Hoxa9 Axis in Establishment of Normal Hematopoietic and Leukemic Stem Cells. Cell Stem Cell, 3 June 2011; 8(6) pp. 649 - 662 DOI: 10.1016/j.stem.2011.05.004, G: b( W% n' j2 T/ O2 i! p7 ]
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（Docofsoul译于2011年6月3日星期五）2 Y, b- n4 v4 x& L1 Q* Y
原英文报道地址：( W8 @2 M8 @& [; h

; p/ X& b  {" O  e& qhttp://www.sciencedaily.com/releases/2011/06/110602122252.htm! E; ~& y# g% e# B5 u7 A
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