Yamamoto Katsuya, Minami Yosuke, Yakushijin Kimikazu, Mizutani Yu, Inui Yumiko, Kawamoto Shinichiro, Matsui Keiji, Nakamachi Yuji, Kawano Seiji, Matsuoka Hiroshi, Minami Hironobu
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Cytogenet Genome Res. 2016;150(3-4):287-292. doi: 10.1159/000458168. Epub 2017 Mar 2.
The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.
t(11;20)(p15;q11∼12)易位是一种非常罕见但反复出现的细胞遗传学异常，发生于骨髓增生异常综合征/急性髓系白血病（MDS/AML）。该易位被证实会在11p15的NUP98和20q12的TOP1之间形成一个融合基因。在此，我们描述了一例新发的伴有t(11;20)的AML M2病例，其与另一种平衡易位相关。一名81岁男性因复发AML入院接受挽救治疗。G显带和光谱核型分析显示为46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]。NUP98/TOP1融合转录本的表达得到证实：NUP98外显子13与TOP1外显子8框内融合。还检测到了相互的TOP1/NUP98融合转录本：TOP1外显子7与NUP98外显子14融合。在获得血液学完全缓解后，核型转变为46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]。荧光原位杂交（FISH）分析表明，t(2;5)的5q31断点位于EGR1的着丝粒侧。在文献报道的所有10例病例中，均表达了NUP98外显子13/TOP1外显子8融合转录本，表明其可能是伴有t(11;20)的MDS/AML发病机制的原因。另一方面，TOP1/NUP98转录本在4例新发AML中共同表达，但在3例治疗相关MDS中未表达。因此，这种相互融合可能与进展为AML有关。
