Open AccessThe partial tandem duplication of ALL1 in acute myeloid leukemia with normal cytogenetics or trisomy 11 is restricted to one chromosome
Author(s) -
Michael A. Caligiuri,
Matthew P. Strout,
Adam R. Oberkircher,
Feng Yu,
Albert de la Chapelle,
Clara D. Bloomfield
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.8.3899
Subject(s) - biology , gene duplication , tandem exon duplication , cytogenetics , genetics , trisomy , chromosomal translocation , gene rearrangement , chromosome , cancer research , gene
The molecular defects responsible for tumorigenesis in adultde novo acute myeloid leukemia (AML) with a normal karyotype or an additional copy of one chromosome (i.e., trisomy) remain largely unknown. We recently discovered that approximately 90% of adult patients withde novo AML and trisomy 11 (+11) as a sole abnormality and 11% of adult patients withde novo AML and normal cytogenetics carry a molecular rearrangement of theALL1 (MLL, HRX, orHTRX ) gene. The rearrangedALL1 gene has been shown to result from the direct tandem duplication of a portion ofALL1 itself. To better understand the underlying mechanisms of leukemogenesis, we asked whether in cytogenetically normal cases one or both chromosomes carry the mutated allele and whether in trisomic cases the mutation is present in one, two, or three chromosomes. Herein we show that in cytogenetically normal cases of AML and in cases with +11 as a sole cytogenetic abnormality, only one chromosome contains the mutatedALL1 allele. Thus a single mutatedALL1 allele with the partial tandem duplication is sufficient forALL1- associated leukemogenesis, irrespective of the number of normal genes present. The frequently occurring specific association of +11 andALL1 gene mutation in the leukemic clone remains unexplained.