title: Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement.
abstract: The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. sly7012@adm.cgmh.org.tw
authors.forename: L-Y
authors.initials: LY
authors.lastname: Shih
authors.forename: D-C
authors.initials: DC
authors.lastname: Liang
authors.forename: J-F
authors.initials: JF
authors.lastname: Fu
authors.forename: J-H
authors.initials: JH
authors.lastname: Wu
authors.forename: P-N
authors.initials: PN
authors.lastname: Wang
authors.forename: T-L
authors.initials: TL
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: Dunn
authors.forename: M-C
authors.initials: MC
authors.lastname: Kuo
authors.forename: T-C
authors.initials: TC
authors.lastname: Tang
authors.forename: T-H
authors.initials: TH
authors.lastname: Lin
authors.forename: C-L
authors.initials: CL
authors.lastname: Lai
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002675:Child, Preschool; D005260:Female; D020440:Gene Duplication; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011446:Prospective Studies; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase