title: MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype.
abstract: Rearrangement of the MLL (myeloid-lymphoid or mixed-lineage leukemia) gene through a reciprocal chromosomal translocation is found in 5% of adult acute myeloid (AML) and 10% of pediatric acute lymphoid (ALL) leukemia. More than 25 different reciprocal chromosomal translocations, with an 11q23 breakpoint, fuse the MLL gene (also named ALL-1, HRX and Htrx1) to a second partner gene. These leukemias have poor prognosis and frequently have a monocytic, lymphoid or biphenotypic (myeloid and lymphoid) antigen expression in blast cells. Approximately 20-30% of patients diagnosed as having adult de novo, AML have normal chromosomes by metaphase analysis and the majority of these patients have good prognosis. With the use of reverse transcriptase-polymerase chain reaction (RT-PCR) technique and Southern blot analysis, we found that seven of 34 such patients (21%) had a tandem partial duplication of exons 2 to 6 or 2 to 8 of the MLL gene. These seven patients showed a median survival of 2.7 months, compared to a 6.8 months median survival for all other patients in the study. If confirmed on a large series of patients, our findings may help differentiate AML with normal karyotype and poor prognosis from those with normal karyotype and a more favorable prognosis.
authors.affiliation: Cancer Biology Division, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Honoki
authors.forename: J
authors.initials: J
authors.lastname: Andersen
authors.forename: E
authors.initials: E
authors.lastname: Paietta
authors.forename: D K
authors.initials: DK
authors.lastname: Nam
authors.forename: J J
authors.initials: JJ
authors.lastname: Yunis
mesh_terms: D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011519:Proto-Oncogenes; D012326:RNA Splicing; D015996:Survival Rate; D014157:Transcription Factors; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase