Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13)

Abstract

The NUP98 gene at 11p15 is known to be fused to DDX10, HOXA9, HOXA11, HOXA13, HOXD11, HOXD13, LEDGF, NSD1, NSD3, PMX1, RAP1GDS1, and TOP1 in various hematologic malignancies. The common theme in all NUP98 chimeras is a transcript consisting of the 5' part of NUP98 and the 3' portion of the partner gene; however, apart from the frequent fusion to different homeobox genes, there is no apparent similarity among the other partners. We here report a de novo acute myeloid leukemia with a t(11;12)(p15;q13), resulting in a novel NUP98/HOXC13 fusion. Fluorescence in situ hybridization analyses, by the use of probes covering NUP98 and the HOXC gene cluster at 12q13, revealed a fusion signal at the der(11)t(11;12), indicating a NUP98/HOXC chimera, whereas no fusion was found on the der(12)t(11;12), suggesting that the translocation was accompanied by a deletion of the reciprocal fusion gene. Reverse transcription-PCR and sequence analyses showed that exon 16 (nucleotide 2290) of NUP98 was fused in-frame with exon 2 (nucleotide 852) of HOXC13. Neither the HOXC13/NUP98 transcript nor the normal HOXC13 was expressed. The present results, together with previous studies of NUP98/homeobox gene fusions, strongly indicate that NUP98/HOXC13 is of pathogenetic importance in t(11;12)-positive acute myeloid leukemia.

NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML-M2

“…The abnormal nuclear location of the fusion protein inside of the nucleus, instead of the normal NUP98 localization at , that covers NUP98, labels normal chromosome 11, der(11) and der (17). RP11 555F1 (green), located~600 Kb telomeric to NUP98, labels normal chromosome 11 and der (17).…”

“…RP11 555F1 (green), located~600 Kb telomeric to NUP98, labels normal chromosome 11 and der (17). (II) RP11 348A20 probe (red), labels normal chromosome 11, der(11) and der (17).…”

“…RP11 555F1 (green), located~600 Kb telomeric to NUP98, labels normal chromosome 11 and der (17). (II) RP11 348A20 probe (red), labels normal chromosome 11, der(11) and der (17). RP5 1112G21 probe (green), that covers CDC6, RARa and TOP2A labels normal chromosome 17 and der (17).…”

“…(II) RP11 348A20 probe (red), labels normal chromosome 11, der(11) and der (17). RP5 1112G21 probe (green), that covers CDC6, RARa and TOP2A labels normal chromosome 17 and der (17).…”

“…To date, NUP98 has been shown to be fused to another 6 class-1 homeobox genes: HOXD13 (2q31) [12], HOXD11 (2q31) [13], HOXA13 (7p15) [14,15], HOXA11 (7p15) [15], HOXC11 (12q13) [16], and HOXC13 (12q13) [17]; and to the class-2 homeobox gene PMX1 (1q23) [18].…”