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11p15 translocations involving theNUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome

1999; Wiley; Volume: 26; Issue: 3 Linguagem: Inglês

10.1002/(sici)1098-2264(199911)26

1098-2264

Mayumi Nishiyama, Yasuhito Arai, Yukiko Tsunematsu, Hirofumi Kobayashi, Keiko Asami, Miharu Yabe, Shunichi Kato, M Oda, Haruhiko Eguchi, Misao Ohki, Yasuhiko Kaneko,

Protein Degradation and Inhibitors

In a survey of childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) in Japan, we found 11p15 translocations in 5 (6%) of 81 children with t-AML/MDS. t(11;17)(p15;q21), t(11;12)(p15;q13), t(7;11)(p15;p15), inv(11)(p15q22), and add(11)(p15) were each found in one patient. Southern blotting and/or RT-PCR analyses revealed rearrangements of the NUP98 gene in tumor samples of all five patients. Rearrangements of DDX10 were detected in t-AML/MDS cells with inv(11), and rearrangements of HOXA9 were detected in t-AML cells with t(7;11). The 17q21 breakpoint of t(11;17) and the 12q13 breakpoint of t(11;12)(p15;q13) coincided with the loci of the HOXB and HOXC gene families, respectively. Therefore, it is reasonable to speculate that one of the HOXB genes and one of the HOXC genes were fused to NUP98 by t(11;17) and t(11;12), respectively, in t-AML/MDS cells. We propose that NUP98 may be a target gene for t-AML/MDS, and that t-AML/MDS with a fusion of NUP98 and HOX or DDX10 genes may be more frequent in children than in patients of other age groups. Genes Chromosomes Cancer 26:215–220, 1999. © 1999 Wiley-Liss, Inc.