Chinen Yoshiaki, Taki Tomohiko, Tsutsumi Yasuhiko, Kobayashi Satoru, Matsumoto Yosuke, Sakamoto Natsumi, Kuroda Junya, Horiike Shigeo, Nishida Kazuhiro, Ohno Hirofumi, Uike Naokuni, Taniwaki Masafumi
Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
Genes Chromosomes Cancer. 2014 Apr;53(4):299-308. doi: 10.1002/gcc.22140. Epub 2014 Jan 21.
The monocytic leukemia zinc finger protein KAT6A (formerly MOZ) gene is recurrently rearranged by chromosomal translocations in acute myeloid leukemia (AML). KAT6A is known to be fused to several genes, all of which have histone acetyltransferase (HAT) activity and interact with a number of transcription factors as a transcriptional coactivator. The present study shows that the leucine twenty homeobox (LEUTX) gene on 19q13 is fused to the KAT6A gene on 8p11 in a therapy-related AML with t(8;19)(p11;q13) using the cDNA bubble PCR method. The fusion transcripts contained 83 nucleotides upstream of the first ATG of LEUTX and are presumed to create in-frame fusion proteins. LEUTX is known to have a homeobox domain. Expression of the LEUTX gene was only detected in placenta RNA by RT-PCR, but not in any tissues by Northern blot analysis. The putative LEUTX protein does not contain any HAT domain, and this is the first study to report that KAT6A can fuse to the homeobox gene. The current study, with identification of a new partner gene to KAT6A in a therapy-related AML, does not elucidate the mechanisms of leukemogenesis in KAT6A-related AML but describes a new gene with a different putative function.
单核细胞白血病锌指蛋白KAT6A（原名MOZ）基因在急性髓系白血病（AML）中经常因染色体易位而发生重排。已知KAT6A与多个基因融合，所有这些基因都具有组蛋白乙酰转移酶（HAT）活性，并作为转录共激活因子与多种转录因子相互作用。本研究表明，在一例伴有t(8;19)(p11;q13)的治疗相关AML中，19q13上的亮氨酸二十同源框（LEUTX）基因与8p11上的KAT6A基因融合，采用cDNA气泡PCR方法进行检测。融合转录本包含LEUTX第一个ATG上游83个核苷酸，推测可产生读码框内融合蛋白。已知LEUTX具有一个同源框结构域。通过RT-PCR仅在胎盘RNA中检测到LEUTX基因表达，而Northern印迹分析在任何组织中均未检测到。推测的LEUTX蛋白不包含任何HAT结构域，这是首次报道KAT6A可与同源框基因融合的研究。当前研究在一例治疗相关AML中鉴定出KAT6A的一个新伙伴基因，但并未阐明KAT6A相关AML的白血病发生机制，而是描述了一个具有不同推测功能的新基因。
