Lappin Terence R J, Grier David G, Thompson Alexander, Halliday Henry L
Haematology Research Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast City Hospital.
Ulster Med J. 2006 Jan;75(1):23-31.
HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21 [corrected] 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary conservation provides unlimited scope for experimental investigation of the functional control of the Hox gene network which is providing important insights into human disease. Chromosomal translocations involving the MLL gene, the human homologue of the Drosophila gene trithorax, create fusion genes which exhibit gain of function and are associated with aggressive leukaemias in both adults and children. To date 39 partner genes for MLL have been cloned from patients with leukaemia. Models based on specific translocations of MLL and individual HOX genes are now the subject of intense research aimed at understanding the molecular programs involved, and ultimately the design of chemotherapeutic agents for leukaemia. Investigation of the role of HOX genes in cancer has led to the concept that oncology may recapitulate ontology, a challenging postulate for experimentalists in view of the functional redundancy implicit in the HOX gene network.
HOX基因在进化上高度保守。它们编码的HOX蛋白是胚胎发育的主要调节因子，并在出生后的整个生命过程中持续表达。39个人类HOX基因分别位于7号染色体p15、17号染色体q21[已修正]、12号染色体q13和2号染色体q31的四个簇（A - D）中，被认为是由一个原始同源框基因通过复制和分化产生的。肢体形成障碍，如手足生殖器综合征，已被追溯到HOXA13和HOXD13的突变。进化保守性为Hox基因网络功能控制的实验研究提供了无限的空间，这为人类疾病提供了重要的见解。涉及MLL基因（果蝇基因三体胸节的人类同源物）的染色体易位产生了具有功能获得性的融合基因，并与成人和儿童的侵袭性白血病相关。迄今为止，已从白血病患者中克隆出39个MLL的伙伴基因。基于MLL和单个HOX基因的特定易位的模型现在是深入研究的主题，旨在了解其中涉及的分子程序，并最终设计白血病的化疗药物。对HOX基因在癌症中的作用的研究导致了肿瘤学可能重现本体论的概念，鉴于HOX基因网络中隐含的功能冗余，这对实验人员来说是一个具有挑战性的假设。
