COMPLEX MLL REARRANGEMENT IN A PATIENT WITH T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA

MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements are uncommon in T-cell ALL We recentl y detected an MLL gene rearrangement in a patient with typical T-cell ALL (CD2(+), CD4(+), CD5(+), CD7(+), CD8(+), HLA DR(-)) and an apparen tly normal karyotype (46,XX). The rearrangement was cloned and charact erized; a DNA fragment distal to the breakpoint was mapped by fluoresc ence in situ hybridization (FISH) to 19p13, indicating that the leukem ic blasts had undergone a cytogenetically undetected rearrangement inv olving chromosomes 11 and 19. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated an in-frame fusion mRNA between the amino terminus of MLL and the carboxy terminus of ENL (also known as MLLTI or LTG19), a gene that has been mapped to 19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were deleted from the genome, which precludes the formation of a reciprocal ENL/MLL fusi on protein. These findings suggest that an MLL/ENL fusion protein (and not a reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they reinforce previous studies showing that leukemic bla sts with apparently normal karyotype may harbor MLL rearrangements. Ad ditionally, this report provides the first conclusive evidence of an M LL/ENL gene fusion characterized at a molecular level in a patient wit h T-cell ALL. (C) 1995 Wiley-Liss, Inc.