Imamura Toshihiko, Kakazu Naoki, Hibi Shigeyoshi, Morimoto Akira, Fukushima Yoko, Ijuin Ikuko, Hada Satoshi, Kitabayashi Issei, Abe Tatsuo, Imashuku Shinsaku
Department of Pediatrics, Kyoto Prefectural University of Medicine, 465 Kaiji-cho, Hirokoji, Kamigyo-ku, Kyoto, Japan.
Genes Chromosomes Cancer. 2003 Apr;36(4):413-9. doi: 10.1002/gcc.10172.
In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French-American-British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient.
在本研究中，我们检查了一例与治疗相关的小儿骨髓增生异常综合征（tMDS）病例。症状在急性髓细胞白血病（AML，根据法美英[FAB]分类为M2亚型）治疗17个月后出现，该AML涉及t(8;21)(q22;q22)染色体异常。在诊断tMDS时，光谱核型分析检测到一个新的染色体易位t(2;8)(p23;p11.2)。此外，荧光原位杂交分析提示位于8号染色体8p11区域的单核细胞白血病锌指（MOZ）基因发生重排。然而，在2p23上未发现配对基因。据我们所知，这是首例与MOZ基因重排相关的tMDS报告。MOZ相关融合蛋白，如MOZ-CBP（CREB结合蛋白）、MOZ-TIF2（转录中介因子2）和MOZ-p300（腺病毒E1A相关蛋白），分别与AML的t(8;16)(p11;p13)、inv(8)(p11q13)和t(8;22)(p11;q13)染色体异常相关，并且被认为是通过组蛋白乙酰化的异常调节导致白血病发生。通过类似机制，我们认为在2p23处与未知配对基因融合的MOZ可能导致了组蛋白乙酰化改变，从而导致该患者发生tMDS。
