Adamaki Maria, Goulielmaki Maria, Christodoulou Ioannis, Vlahopoulos Spiros, Zoumpourlis Vassilis
Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece.
Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece; Horemio Research Institute, First Department of Pediatrics, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Crit Rev Oncog. 2017;22(3-4):157-185. doi: 10.1615/CritRevOncog.2017024465.
Homeobox (HOX) genes are a superfamily of highly conserved genes with essential functions in many aspects of mammalian development. Their expression is tightly regulated throughout the duration of definitive hematopoiesis, so the pathogenetic mechanism that leads to leukemia suggests that malignant transformation is directly intertwined with the deregulation of HOX gene expression. Even though HOX gene involvement has been reviewed extensively in adult leukemias, childhood leukemias have received much less attention and mainly in the context of leukemias harboring MLL (mixed-lineage leukemia) gene translocations. In recent years, scientific evidence has highlighted HOX gene involvement in the development of other subtypes of childhood leukemias and added HOX gene family members that were previously unrelated to the pathogenesis of childhood leukemia. This has significant implications when considering both the risk stratification of pediatric patients and potential targets for successful therapy. Through the identification of HOX target genes, their resulting interactions, and the cognate signaling pathways, we hope to gain a better understanding of the molecular mechanism(s) underlying the ectopic activation of these genes in childhood leukemias and subsequently to reveal new molecular targets for successful therapy in cases of poor prognosis or resistant disease.
同源盒（HOX）基因是一个高度保守的基因超家族，在哺乳动物发育的许多方面具有重要功能。在确定性造血过程中，它们的表达受到严格调控，因此导致白血病的致病机制表明，恶性转化与HOX基因表达失调直接相关。尽管HOX基因在成人白血病中的作用已得到广泛综述，但儿童白血病受到的关注较少，主要是在伴有混合谱系白血病（MLL）基因易位的白血病背景下。近年来，科学证据突显了HOX基因在其他儿童白血病亚型发生中的作用，并增加了以前与儿童白血病发病机制无关的HOX基因家族成员。这在考虑儿科患者的风险分层和成功治疗的潜在靶点时具有重要意义。通过鉴定HOX靶基因、它们产生的相互作用以及相关信号通路，我们希望更好地理解这些基因在儿童白血病中异位激活的分子机制，进而揭示预后不良或耐药病例成功治疗的新分子靶点。
