Coexistence of LMPP-like and GMP-like Leukemia Stem Cells in Acute Myeloid Leukemia
Coexistence of LMPP-like and GMP-like Leukemia Stem Cells in Acute Myeloid Leukemia
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DOI：
10.1016/j.ccr.2010.12.012
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发表时间：
2011-01-18
期刊：
影响因子：
50.3
通讯作者：
Vyas, Paresh
中科院分区：
文献类型：
--
作者：
Goardon, Nicolas;Marchi, Emanuele;Vyas, Paresh
正常干细胞/祖细胞与白血病干细胞/祖细胞之间的关系尚不明确。我们发现，在约80%的原发性人类CD34(+)急性髓系白血病（AML）中，大多数患者体内同时存在两种具有造血祖细胞免疫表型的扩增群体。这两种群体都具有白血病干细胞（LSC）活性，且呈层级排列；一种白血病干细胞群体可产生另一种。全基因表达谱分析显示，白血病干细胞群体在分子层面上存在差异，它们类似于正常祖细胞，但不同于干细胞。更成熟的白血病干细胞群体与正常的粒细胞 - 巨噬细胞祖细胞（GMP）最为相似，而不成熟的白血病干细胞群体则是一种此前未被描述的祖细胞，其功能类似于淋巴细胞预激多能祖细胞（LMPPs）。这表明在大多数情况下，原发性CD34(+)急性髓系白血病是一种祖细胞疾病，其中白血病干细胞获得了异常的自我更新潜能。
The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in similar to 80% of primary human CD34(+) acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34(+) AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.