Recurring chromosomal translocations involving chromosome 11, band q23, have been observed in acute lymphoid leukemias and especially in acute myeloid leukemias. We recently showed that breakpoints in four 11q23 translocations, t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13.3), were contained within a yeast artificial chromosome done bearing the CD3D and CD3G gene loci. We have identified within the CD3 yeast artificial chromosome a transcription unit that spans the breakpoint junctions of the 4;11, 9;11, and 11;19 translocations, and we describe two other, related transcripts that are upregulated in the RS4;11 cell line. We have named this gene MLL (myeloid/lymphoid, or mixed-fineage, leukemia).

Recurring chromosomal abnormalities Involving translocations at chromosome 11 band q23 are associated with human myelold and lymphold leukemia as well as lymphoma. We have Identified the gene located at this breakpoint and have named it MLL (for myeloidlymphold, or mixed-lineage, leukemia). The t(4;11), t(6;11), t(9;11), and t(11;19) are among the most common reciprocal translocathons in leukemia cells involving this chromosomal band. We now have evidence that the breakpoints in all of these translocations are clustered within a 9-kilobase (kb) BamHI genomic region of the MLL gene. By Southern blot hybridization using a 0.7-kb BamEH cDNA fgnt of the MLL gene called MLL 0.7B, we have detected rearrangements of DNA from cell ln and patient material with an 11q23 trandocation in this region.Northern blot analyses dicte that this gene has multipl cpts, some of which appear to be lineage-specific. In normal pre-B cells, four transcripts of 12.5, 12.0, 11.5, and 2.0 kb are detected. These tanscripts are also present in monocytoid cell lines with additional hybridization to a 5.0-kb t rpt, indicating that expression of different-sized MLL transcripts may be associated with normal hematopoietic lineage development. In a cell Hlne with a t(4;11), the expression of the 12.5-, 12.0-, and 11.5-kb transcripts is reduced, and there is evidence of three other altered transcripts of 11.5, 11.25, and 11.0 kb. Thus, these 11q23 translocations result in rearrangements of the MLL gene and may lead to altered function(s) of MLL and of other gene(s) involved in the translocation.Nonrandom translocations involving chromosome 11 band q23 occur frequently in both myeloid and lymphoblastic leukemias (1, 2). The four most common reciprocal translocations are t(4;11) and t(11;19), which often exhibit either lymphoblastic and/or monocytic markers, and t(6;11) and t(9;11), which are mainly found in monoblastic and/or myeloblastic leukemias (3). Other chromosomes which are involved in recurring translocations with this band in acute leukemias are chromosomes X, 1, 2, 10, and 17. Fluorescence in situ hybridization showed that a yeast artificial chromosome containing the CD3D and CD3G genes was split in cells with the four most common translocations (4). We identified the gene located at the breakpoint and we named it MLL (5). Recent data indicate that the breakpoint in a cell line, RC-K8, with a t(11;14)(q23;q32) is -110 kilobases (kb) telomeric to the breakpoint in other 11q23 translocations which involve the MLL gene (6)(7)(8). Our data support this finding and suggest that there are at least two different regions of band q23 involved in chromosome 11q23 translocations; we distinguish these by using the term "more centromeric" to designate MLL rearrangements from those involving the more telomeric breakpoint, which has been described as the rck locus (6) and the p54 gene (7).By pulsed-field gel electrophoresis analyses, the breakpoint region in MLL was mapped to a 92-kb Not I fragment -=100 kb telomeric to the CD3G gene. Nonrepetitiv...