Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23
Journal
Leukemia
Journal Volume
16
Journal Issue
2
Pages
196-202
Date Issued
2002
Author(s)
Shiah H.-S.
Kuo Y.-Y.
Wang D.-T. C.-H. -au Shen, Lin K.-H.
Abstract
The clinical and biological features of acute myeloid leukemia (AML) with 11q23/MLL translocations are well known, but the characteristics of AML with partial tandem duplication of the MLL gene have not been explored comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA polymerase chain reaction (PCR), reverse-transcription PCR and complementary DNA sequencing. Nine patients showed partial tandem duplication of the MLL gene, including eight (12%) of the 68 with normal karyotype. Seven patients showed fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs 6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had a significantly higher incidence of CD11b expression on leukemic cells than did those without in the subgroup of patients with normal karyotype (75% vs 28%, P = 0.017). There were no significant differences in the expression of lymphoid antigens or other myeloid antigens between the two groups of patients. In adults, the patients with MLL duplication had a shorter median survival time than those without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients. The higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.
Other Subjects
CD11b antigen; genomic DNA; mixed lineage leukemia protein; acute granulocytic leukemia; adolescent; adult; aged; antigen expression; article; cancer survival; child; chromosome 11q; chromosome analysis; controlled study; DNA sequence; DNA splicing; DNA transcription; exon; female; gene duplication; human; human cell; incidence; infant; karyotype; leukemia cell; leukemogenesis; major clinical study; male; polymerase chain reaction; priority journal; prognosis; reverse transcription polymerase chain reaction; Southern blotting; structural chromosome aberration; survival time
Type
journal article