title: ML-1 cell line lacks a germline MLL locus.
abstract: Gene rearrangements involving MLL (also known as ALL1, HRX, or Htrx) are among the most common molecular abnormalities associated with acute leukemia. These leukemias generally have one allele involved in a rearrangement, while the remaining allele is uninvolved and demonstrates a germline MLL configuration. In this study, we describe a leukemic cell line that does not have a germline MLL allele and thus cannot produce a normal MLL gene product. We show that the ML-1 cell 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. Cloning of the genomic breakpoints on the derivative(6) and der(11) chromosomes demonstrated a balanced translocation between MLL on chromosome band 11q23 and AF6 on chromosome band 6q27. Sequence analysis of the derivative chromosomes revealed that a 186-bp segment of MLL intron 6, downstream of the breakpoint, had been duplicated, inverted, and inserted 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 allele demonstrates that a normal MLL gene is not required for survival, proliferation, or differentiation of this cell line.
authors.affiliation: Division of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Strout
authors.forename: K
authors.initials: K
authors.lastname: Mrózek
authors.forename: K
authors.initials: K
authors.lastname: Heinonen
authors.forename: S N
authors.initials: SN
authors.lastname: Sait
authors.forename: T B
authors.initials: TB
authors.lastname: Shows
authors.forename: P D
authors.initials: PD
authors.lastname: Aplan
mesh_terms: D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D002871:Chromosome Banding; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase