新研究证明CML如何进展到急性转化期
http://www.100md.com
2004年8月17日
生物谷报道 具有自我更新能力的白血病干细胞被认为在从慢性髓样白血病(CML)到急性转化期的进展中起了某种重要作用。如今新研究表明这些细胞是使用β-catenin信号通路来进行自我更新的。
美国斯坦福大学的威斯曼(Irving L. Weissman)和同事在8月12日《新英格兰医学杂志》(N Engl J Med 2004;351:634-636,657-667)上报告，他和同事使用多种技术来比较了从59名CML病人和11名健康对照者身上得到的粒细胞——巨噬细胞系祖细胞。在CML病人中，20人为慢性期，26人为加速期，13人为急性转化期。
与从对照者身上得到的细胞相比，CML急性转化期病人和对伊马替尼有抵抗性的病人的粒细胞-巨噬细胞干细胞库增大，表达有BCR-ABL，核β-catenin水平增高。与正常血液干细胞不同，白血病干细胞形成了明显的有自我更新力的髓样克隆。另外，白血病干细胞的自我更新能力随axin蛋白的表达增强而降低。
, http://www.100md.com
这些结果表明“β-catenin信号通路中的组分，特别是突变的组分，可能是研制CML分子和免疫治疗方法的新靶标”，作者指出。
“多数急性转化期的治疗是按其从骨髓中清除祖细胞的能力来选择的”，密歇根大学的克拉克(Michael F. Clarke)在相关评论中说，“但是，自我更新的祖细胞似乎是急性转化期的潜在原因，因为治疗未直接针对它们，这些原始细胞――就象一条有多个头的怪蛇一样――可以持续补充骨髓中的祖细胞系”。
ORIGINAL TEXT：
New Findings Shed Light on How CML Progresses to Blast Crisis
August 12, 2004 (Reuters) -
, 百拇医药
NEW YORK - Self-renewing leukemic stem cells are thought to play an important role in the progression of chronic myelogenous leukemia (CML) to blast crisis. Now, new research suggests that these cells use the beta-catenin-signaling pathway for self-renewal.
As reported in the Aug. 12 issue of The New England Journal of Medicine, Dr. Irving L. Weissman, from Stanford University in California, and colleagues used various techniques to compare granulocyte-macrophage progenitors obtained from 59 CML patients and 11 healthy controls. Of the CML patients, 20 had chronic phase disease, 26 had accelerated-phased CML, and 13 were in blast crisis.
, 百拇医药
Compared with cells from control subjects, the granulocyte-macrophage stem cell pool from CML patients in blast crisis and those with imatinib-resistant disease was expanded, expressed BCR-ABL, and displayed increased levels of nuclear beta-catenin.
Unlike normal hemapoietic stem cells, the leukemic progenitors formed distinct self-renewing myeloid colonies, the researchers note. In addition, the self-renewing capacity of the leukemic stem cells decreased with enforced expression of axin.
, http://www.100md.com
The results suggest that "components of the beta-catenin-signaling pathway, especially ones that are mutated, may provide new targets for the development of molecular and immune therapies for CML," the authors point out.
"Most treatments for blast crisis are chosen for their ability to eliminate blasts from the bone marrow," Dr. Michael F. Clarke, from the University of Michigan in Ann Arbor, notes in a related editorial.
"However, since self-renewing blast-crisis progenitors appear to underlie the crisis, these progenitors -- like a Hydra with a severed head -- continue to replenish the population of blasts in the marrow because the treatment is not directed against them.", 百拇医药
美国斯坦福大学的威斯曼(Irving L. Weissman)和同事在8月12日《新英格兰医学杂志》(N Engl J Med 2004;351:634-636,657-667)上报告，他和同事使用多种技术来比较了从59名CML病人和11名健康对照者身上得到的粒细胞——巨噬细胞系祖细胞。在CML病人中，20人为慢性期，26人为加速期，13人为急性转化期。
与从对照者身上得到的细胞相比，CML急性转化期病人和对伊马替尼有抵抗性的病人的粒细胞-巨噬细胞干细胞库增大，表达有BCR-ABL，核β-catenin水平增高。与正常血液干细胞不同，白血病干细胞形成了明显的有自我更新力的髓样克隆。另外，白血病干细胞的自我更新能力随axin蛋白的表达增强而降低。
, http://www.100md.com
这些结果表明“β-catenin信号通路中的组分，特别是突变的组分，可能是研制CML分子和免疫治疗方法的新靶标”，作者指出。
“多数急性转化期的治疗是按其从骨髓中清除祖细胞的能力来选择的”，密歇根大学的克拉克(Michael F. Clarke)在相关评论中说，“但是，自我更新的祖细胞似乎是急性转化期的潜在原因，因为治疗未直接针对它们，这些原始细胞――就象一条有多个头的怪蛇一样――可以持续补充骨髓中的祖细胞系”。
ORIGINAL TEXT：
New Findings Shed Light on How CML Progresses to Blast Crisis
August 12, 2004 (Reuters) -
, 百拇医药
NEW YORK - Self-renewing leukemic stem cells are thought to play an important role in the progression of chronic myelogenous leukemia (CML) to blast crisis. Now, new research suggests that these cells use the beta-catenin-signaling pathway for self-renewal.
As reported in the Aug. 12 issue of The New England Journal of Medicine, Dr. Irving L. Weissman, from Stanford University in California, and colleagues used various techniques to compare granulocyte-macrophage progenitors obtained from 59 CML patients and 11 healthy controls. Of the CML patients, 20 had chronic phase disease, 26 had accelerated-phased CML, and 13 were in blast crisis.
, 百拇医药
Compared with cells from control subjects, the granulocyte-macrophage stem cell pool from CML patients in blast crisis and those with imatinib-resistant disease was expanded, expressed BCR-ABL, and displayed increased levels of nuclear beta-catenin.
Unlike normal hemapoietic stem cells, the leukemic progenitors formed distinct self-renewing myeloid colonies, the researchers note. In addition, the self-renewing capacity of the leukemic stem cells decreased with enforced expression of axin.
, http://www.100md.com
The results suggest that "components of the beta-catenin-signaling pathway, especially ones that are mutated, may provide new targets for the development of molecular and immune therapies for CML," the authors point out.
"Most treatments for blast crisis are chosen for their ability to eliminate blasts from the bone marrow," Dr. Michael F. Clarke, from the University of Michigan in Ann Arbor, notes in a related editorial.
"However, since self-renewing blast-crisis progenitors appear to underlie the crisis, these progenitors -- like a Hydra with a severed head -- continue to replenish the population of blasts in the marrow because the treatment is not directed against them.", 百拇医药