Olsson Linda, Johansson Bertil
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Br J Haematol. 2015 May;169(4):479-91. doi: 10.1111/bjh.13342. Epub 2015 Mar 5.
The IKZF1 gene at 7p12.2 codes for IKAROS (also termed IKZF1), an essential transcription factor in haematopoiesis involved primarily in lymphoid differentiation. Its importance is underlined by the fact that deregulation of IKAROS results in leukaemia in both mice and men. During recent years, constitutional as well as acquired genetic changes of IKZF1 have been associated with human disease. For example, certain germline single nucleotide polymorphisms in IKZF1 have been shown to increase the risk of some disorders and abnormal expression and somatic rearrangements, mutations and deletions of IKZF1 (ΔIKZF1) have been detected in a wide variety of human malignancies. Of immediate clinical importance is the fact that ΔIKZF1 occurs in 15% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL) and that the presence of ΔIKZF1 is associated with an increased risk of relapse and a poor outcome; in some studies such deletions have been shown to be an independent risk factor also when minimal residual disease data are taken into account. However, cooperative genetic changes, such as ERG deletions and CRLF2 rearrangements, may modify the prognostic impact of ΔIKZF1, for better or worse. This review summarizes our current knowledge of IKZF1 abnormalities in human disease, with an emphasis on BCP ALL.
位于7p12.2的IKZF1基因编码IKAROS（也称为IKZF1），它是造血过程中一种重要的转录因子，主要参与淋巴细胞分化。IKAROS失调会导致小鼠和人类患白血病，这一事实凸显了它的重要性。近年来，IKZF1的遗传性以及后天性基因变化都与人类疾病有关。例如，IKZF1中某些种系单核苷酸多态性已被证明会增加某些疾病的风险，并且在多种人类恶性肿瘤中都检测到了IKZF1的异常表达、体细胞重排、突变和缺失（ΔIKZF1）。具有直接临床重要性的是，ΔIKZF1出现在15%的儿童B细胞前体急性淋巴细胞白血病（BCP ALL）中，并且ΔIKZF1的存在与复发风险增加和不良预后相关；在一些研究中，即使考虑到微小残留病数据，这种缺失也被证明是一个独立的危险因素。然而，诸如ERG缺失和CRLF2重排等协同基因变化可能会改变ΔIKZF1的预后影响，可能变好也可能变差。这篇综述总结了我们目前对人类疾病中IKZF1异常的认识，重点是BCP ALL。
