ML-I CELL-LINE LACKS A GERMLINE MLL LOCUS

Gene rearrangements involving MLL (also known as ALLI, HRX, or Htrx) a re among the most common molecular abnormalities associated with acute leukemia These leukemias generally have one allele involved in a rear rangement, while the remaining allele is uninvolved and demonstrates a germline MLL configuration. In this study, we describe a leukemic cel l line that does not have a germline MLL allele and thus cannot produc e a normal MLL gene product. We show that the ML-1 fell line, derived from a patient with acute myeloid leukemia, has one allele involved in a t(6;11)(q27;q23), while the remaining MLL allele is deleted. Clonin g of the genomic breakpoints on the derivative(6) and der(11) chromoso mes demonstrated a balanced translocation between MLL on chromosome ba nd 11q23 and AF6 on chromosome band 6q27. Sequence analysis of the der ivative chromosomes revealed that a 186-bp segment of MLL intron 6, do wnstream of the breakpoint, had been duplicated, inverted, and inserte d between MLL and AF6 on the der(11) chromosome. In light of the fact that ML-1 cells can be induced to differentiate along the granulocyte and macrophage lineages, the finding that ML-1 lacks a germline MLL al lele demonstrates that a normal MLL gene is not required for survival, proliferation, or differentiation of this cell line. (C) 1996 Wiley-L iss, Inc.