NUP98-HOXD13 Gene Fusion in Therapy-related Acute Myelogenous Leukemia1

A novel chromosomal translocation, t(2;ll)(q31;pl5), was identified in a patient with therapy-related acute myelogenous leukemia (I-AMI.). Fluorescence in \iin hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplifi cation of cDNA ends to identify a chimi-rie iiiKN A. An in-frame, chimeric mRNA that fused NVP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NVP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with I-AMI,, raises the possibility that NVP98 may be a previously un suspected target for chromosomal translocations in patients with t-AMI ..