Abstract
The formation of a leukemogenic fusion product in hematopoietic malignancies is commonly achieved by chromosomal translocation. Alternate and cytogenetically undetectable mechanisms of fusion transcript generation have been documented for BCR–AB1, AML1–ETO, PML–RARA, NPM/ALK, and MLL–MLLT2 (AF4). Here, we report the investigation of a cryptic rearrangement leading to MLL–MLLT3 transcript formation. Cytogenetic analysis of peripheral blood from a 50‐year‐old acute myeloid leukemia patient yielded a karyotype of 47,XY,+8,del(11)(q21q23) in all metaphase cells examined. Metaphase fluorescence in situ hybridization analysis using the MLL probe at 11q23 revealed that the 5′ portion of the MLL gene was inserted into chromosome 9 at band p22, whereas the 3′ region of the MLL gene remained on chromosome 11. Whole‐chromosome paint analysis confirmed the cryptic transfer of chromosome 11 material to 9p22. With this information, the karyotype was reassigned as 47,XY,+8,der(9)ins(9;11)(p22;q23q23),del(11)(q21q23). RT‐PCR was used to show that the cryptic rearrangement in this patient led to the fusion of the MLL and MLLT3 transcripts on the der(9). The presence of the MLL–MLLT3 transcript is consistent with the clinical findings in this patient. © 2004 Wiley‐Liss, Inc.