title: A novel variant form of MLL-ELL fusion transcript with t(11;19)(q23;p13.1) in chronic myelomonocytic leukemia transforming to acute myeloid leukemia.
abstract: MLL located at 11q23 is fused with a variety of partner genes by recurrent chromosomal translocations in acute leukemias. ELL, the MLL partner gene located on chromosome 19p13.1, encodes an RNA polymerase II transcriptional elongation factor, which also possesses the N-terminal region involved in the inhibition of transcription initiation. Here we report a case of chronic myelomonocytic leukemia (CMML) with a 46,XY,t(11;19)(q23;p13.1) karyotype that transformed to acute myeloid leukemia (AML) without showing any karyotypic evolution. Interphase fluorescent in situ hybridization analysis showed the split MLL signals in 95% of bone marrow cells when the diagnosis of CMML was made and the percentage of blasts was 1.2%. Sequence analysis of reverse-transcriptional polymerase chain reaction product revealed a novel variant form of MLL-ELL transcript in which MLL exon 10 was fused to ELL exon 3. MLL has been fused to ELL exon 2 in all the previously reported MLL-ELL transcripts, which have always been associated with AML. It is deduced that the variant form of MLL-ELL may be defective not only in inhibition of transcription initiation, but also in transcriptional elongation. Thus, a possibility is raised that the unique clinical presentation of the present case with t(11;19)(q23;p13.1) might be related to the variant form of MLL-ELL.
authors.affiliation: Department of Hematology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113-8519, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kakihana
authors.forename: Fumito
authors.initials: F
authors.lastname: Kubo
authors.forename: Shihoko
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kurosu
authors.forename: Tohru
authors.initials: T
authors.lastname: Miki
authors.forename: Naomi
authors.initials: N
authors.lastname: Murakami
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
mesh_terms: D000368:Aged; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D018450:Disease Progression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C472772:MLL-ELL fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein