title: A variant-type MLL/SEPT9 fusion transcript in adult de novo acute monocytic leukemia (M5b) with t(11;17)(q23;q25).
abstract: As a result of recurrent chromosomal translocations in acute leukemias, the mixed-lineage-leukemia (MLL) gene fuses with a variety of partner genes, which include several members of the septin gene family. SEPT9 is a very rare but recurrent fusion partner of MLL, and has recently been implicated in the oncogenesis of various malignancies. Herein, we report a case of de novo acute monocytic leukemia (M5b) with t(11;17)(q23;q25). MLL involvement was revealed by fluorescent in situ hybridization (FISH) analysis, and an MLL/SEP9 fusion transcript was detected by RT-PCR. Sequencing analysis further showed that, in contrast to originally reported cases, MLL exon 8 was fused not with SEPT9 exon 3 but with exon 2, which codes for the unique N-terminal region of the SEPT9_v1 isoform, the region implicated in the regulation of gene expression and cell proliferation. We did not detect any mutation of FLT3, which was expressed at a relatively low level in the leukemic cells. Relapsing after a very short complete remission, the leukemia progressed rapidly and became fatal in spite of intensive therapies including hematopoietic stem cell transplantation. It is thus suggested that, in common with the original MLL/SEPT9 cases, monocytic differentiation and a poor prognosis may also be associated with acute myeloid leukemia with the variant MLL/SEPT9 fusion transcript.
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan. tkurosu.hema@tmd.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kurosu
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.|Laboratory Molecular Genetics of Hematology, Graduate School of Health Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohki
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kakihana
authors.affiliation: Laboratory Molecular Genetics of Hematology, Graduate School of Health Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minatoku, Tokyo, 105-8470, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D017809:Fatal Outcome; D020558:GTP Phosphohydrolases / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D058112:Septins; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins