A variant-type MLL/SEPT9 fusion transcript in adult de novo acute monocytic leukemia (M5b) with t(11;17)(q23;q25).
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.
Kurosu
Tetsuya
T
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan. tkurosu.hema@tmd.ac.jp.
Tsuji
Kana
K
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.
Ohki
Manabu
M
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
Miki
Tohru
T
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
Yamamoto
Masahide
M
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
Kakihana
Kazuhiko
K
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
Koyama
Takatoshi
T
Laboratory Molecular Genetics of Hematology, Graduate School of Health Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
Taniguchi
Shuichi
S
Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minatoku, Tokyo, 105-8470, Japan.
Miura
Osamu
O
Department of Hematology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8519, Japan.
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
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