11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome.
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.
Nishiyama
M
M
The Third Clinical Department and Department of Cancer Chemotherapy, Saitama Cancer Center Hospital, Saitama, Japan.
Arai
Y
Y
Tsunematsu
Y
Y
Kobayashi
H
H
Asami
K
K
Yabe
M
M
Kato
S
S
Oda
M
M
Eguchi
H
H
Ohki
M
M
Kaneko
Y
Y
D000208:Acute Disease; D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002880:Chromosomes, Human, Pair 11; D005260:Female; D006801:Humans; D007564:Japan; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C093350:nuclear pore complex protein 98