Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis
Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis
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DOI：
10.1182/blood-2009-07-234559
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发表时间：
2010-10-14
期刊：
影响因子：
20.3
通讯作者：
Ren, Ruibao
中科院分区：
文献类型：
--
作者：
Jo, Seung-Hee;Schatz, Jonathan H.;Ren, Ruibao
干扰素调节因子4 （IRF-4）在b细胞和t细胞发育和免疫反应调节中发挥重要作用，最初被确定为参与多发性骨髓瘤染色体易位的原癌基因的产物。尽管IRF-4在髓细胞中表达，但其在髓细胞谱系中的功能尚不清楚。密切相关的家族成员IRF-8是骨髓生成的关键调节因子，当在小鼠中缺失时，会导致与人类慢性骨髓性白血病高度相似的综合征。在早期淋巴细胞发育中，我们已经证明IRF-4和IRF-8可以发挥冗余功能。因此，我们研究了IRF-4和IRF-8联合缺失对血液学肿瘤发生的影响。我们发现，与单独缺乏IRF-8的小鼠相比，同时缺乏IRF-4和IRF-8的小鼠在很小的时候就会患上一种更具侵袭性的慢性骨髓性白血病样疾病，这与粒细胞单核细胞祖细胞的更大扩张有关。尽管这些结果首次证明IRF-4可以在髓细胞中作为肿瘤抑制因子发挥作用，但有趣的是，所有IRF-4和IRF-8均缺乏的小鼠最终都会发展并死于b淋巴母细胞白血病/淋巴瘤。因此，IRF-4和IRF-8的联合缺失可以协同髓系和淋巴系肿瘤的发展。(血。2010;116 (15):2759 - 2767)
Interferon regulatory factor 4 (IRF-4) plays important functions in B-and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a very early age a more aggressive chronic myelogenous leukemia-like disease than mice deficient in IRF-8 alone, correlating with a greater expansion of granulocyte-monocyte progenitors. Although these results demonstrate, for the first time, that IRF-4 can function as tumor suppressor in myeloid cells, interestingly, all mice deficient in both IRF-4 and IRF-8 eventually develop and die of a B-lymphoblastic leukemia/lymphoma. Combined losses of IRF-4 and IRF-8 therefore can cooperate in the development of both myeloid and lymphoid tumors. (Blood. 2010;116(15):2759-2767)