Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Leukemia. 2010 Oct;24(10):1676-85. doi: 10.1038/leu.2010.177. Epub 2010 Aug 26.
Acute lymphoblastic leukemia (ALL) is a heterogeneous disease comprising multiple subtypes with different genetic alterations and responses to therapy. Recent genome-wide profiling studies of ALL have identified a number of novel genetic alterations that target key cellular pathways in lymphoid growth and differentiation and are associated with treatment outcome. Notably, genetic alteration of the lymphoid transcription factor gene IKZF1 is a hallmark of multiple subtypes of ALL with poor prognosis, including BCR-ABL1-positive lymphoid leukemia and a subset of 'BCR-ABL1-like' ALL cases that, in addition to IKZF1 alteration, harbor genetic mutations resulting in aberrant lymphoid cytokine receptor signaling, including activating mutations of Janus kinases and rearrangement of cytokine receptor-like factor 2 (CRLF2). Recent insights from genome-wide profiling studies of B-progenitor ALL and the potential for new therapeutic approaches in high-risk disease are discussed.
急性淋巴细胞白血病（ALL）是一种异质性疾病，包括多种具有不同遗传改变和治疗反应的亚型。最近对 ALL 的全基因组分析研究确定了一些新的遗传改变，这些改变靶向淋巴样生长和分化的关键细胞途径，并与治疗结果相关。值得注意的是，淋巴样转录因子基因 IKZF1 的遗传改变是多种预后不良的 ALL 亚型的标志，包括 BCR-ABL1 阳性淋巴白血病和一部分“BCR-ABL1 样”ALL 病例，除了 IKZF1 改变外，这些病例还存在导致异常淋巴细胞因子受体信号的遗传突变，包括 Janus 激酶的激活突变和细胞因子受体样因子 2（CRLF2）的重排。本文讨论了来自 B 前体细胞 ALL 的全基因组分析研究的新见解，以及高危疾病中潜在的新治疗方法。
