Back to Search
Start Over
Acute myeloid leukemia with t(7;21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1-DTX2 chimera.
- Source :
-
International journal of hematology [Int J Hematol] 2012 Aug; Vol. 96 (2), pp. 268-73. Date of Electronic Publication: 2012 Jun 04. - Publication Year :
- 2012
-
Abstract
- The RUNX1 gene is frequently rearranged in acute leukemia. We cloned a novel RUNX1 chimeric gene generated by t(7;21)(q11.2;q22) in a patient with acute myeloid leukemia. 3'-rapid amplification of cDNA ends analysis showed a tail-to-tail fusion between RUNX1 on 21q22 and DTX2 on 7q11.2, with an insertion of short complementary sequence from UPK3B adjacent to DTX2. DTX2 encodes a putative E3-ubiquitin ligase with no known biological function. There are two possible functions of RUNX1-reversed UPK3B-DTX2: one from aberrant RUNX1 chimeric protein and the other from the reversed sequence of DTX2. The predicted aberrant protein expressed under the RUNX1 promoter was highly structurally similar to RUNX1a. In a reporter assay, the aberrant protein inhibited the trans-activation function of RUNX1 in a dominant-negative manner, similar to RUNX1a. In contrast, the DTX2 reversed sequence may degrade wild-type DTX2 transcript or suppress its translation. In conclusion, we identified a novel fusion RUNX1 partner, DTX2, which chimerize in a reverse direction. This is the first example of RUNX1 chimera in an opposing direction generated by chromosomal translocation in leukemia. In addition to the aberrantly truncated RUNX1 protein, the DTX2 antisense sequence may play some role in the development of leukemia carrying the t(7;21) translocation.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Aged, 80 and over
Chromosome Banding
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 7
Core Binding Factor Alpha 2 Subunit metabolism
Female
Gene Order
Humans
Leukemia, Myeloid, Acute metabolism
Oncogene Proteins, Fusion metabolism
Ubiquitin-Protein Ligases
Adaptor Proteins, Signal Transducing genetics
Core Binding Factor Alpha 2 Subunit genetics
Gene Expression
Leukemia, Myeloid, Acute genetics
Oncogene Proteins, Fusion genetics
Translocation, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1865-3774
- Volume :
- 96
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 22661044
- Full Text :
- https://doi.org/10.1007/s12185-012-1112-z