title: MLL/SEPTIN6 chimeric transcript from inv ins(X;11)(q24;q23q13) in acute monocytic leukemia: report of a case and review of the literature.
abstract: Rearrangements of the MLL gene on chromosome 11, band q23, are one of the most common genetic changes in acute leukemia. Reciprocal translocation is the most common form of MLL rearrangement, and the partner genes in MLL translocation are notably diverse. Involvement of the SEPTIN6 gene on Xq24 in MLL rearrangements occurs very rarely, with only six cases having been documented in the literature. Of note, the MLL/SEPTIN6 rearrangements in these cases were cryptic or complex, and it was shown that the 5'-MLL/SEPTIN6-3' transcript resides on the derivative X chromosome rather than on the derivative chromosome 11 as in the majority of cases of MLL translocations. These observations suggested that MLL and SEPTIN6 reside on their respective chromosome loci in reverse orientation, that is, centromere-to-telomere and telomere-to-centromere, respectively. We here report a case of acute monocytic leukemia with inv ins(X;11)(q24;q23q13) in a 29-month-old child. Fluorescence in situ hybridization study revealed the break-apart 5'-MLL segment to be translocated to the derivative X chromosome, and reverse transcriptase-polymerase chain reaction followed by sequencing analysis confirmed the 5'-MLL/SEPTIN6-3' chimeric transcript. This case is the first to provide direct cytogenetic evidence for the salient nature of the MLL/SEPTIN6 rearrangement. We reviewed clinical and cytogenetic features of all cases of 11q23 and Xq22-24 rearrangements reported up to now, including six cases where the involvement of the SEPTIN6 gene was confirmed by molecular techniques.
authors.affiliation: Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Quehn
authors.initials: Q
authors.lastname: Park
authors.forename: Hong-Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Keon-Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Kim
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011519:Proto-Oncogenes; D058112:Septins; D014157:Transcription Factors; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D019204:GTP-Binding Proteins; C436485:SEPTIN6 protein, human; D058112:Septins