Abstract
Translocations involving the mixed-lineage leukemia gene (MLL) confer a poor prognosis in acute leukemias. In t(1;11)(q21;q23), MLL is fused reciprocally with AF1q. Here we describe a t(1;11)(q21;q23) with a secondary event involving insertion of the telomeric portion of MLL into the p arm of chromosome 11 (11p11). We show that this latter event interrupts the CUG triplet repeat binding protein-1 (CUGBP1) gene, a translational enhancer of C/EBPbeta. We then showed that these cells have reduced expression of CUGBP1 and C/EBPbeta when compared to other AML blasts. This is the first report to describe insertional disruption of the CUGBP1 gene and to suggest a role for the CUGBP1-C/EBPbeta pathway in leukemogenesis.
Publication types
-
Case Reports
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acute Disease
-
Base Sequence
-
Blotting, Western
-
CCAAT-Enhancer-Binding Protein-beta / antagonists & inhibitors*
-
CCAAT-Enhancer-Binding Protein-beta / genetics
-
CCAAT-Enhancer-Binding Protein-beta / metabolism
-
CELF1 Protein
-
Child
-
Chromosomes, Human, Pair 1 / genetics
-
Chromosomes, Human, Pair 11 / genetics
-
Female
-
Gene Expression Regulation, Neoplastic*
-
Gene Rearrangement*
-
Histone-Lysine N-Methyltransferase
-
Humans
-
In Situ Hybridization, Fluorescence
-
Infant
-
Karyotyping
-
Leukemia, Myeloid / genetics*
-
Leukemia, Myeloid / metabolism
-
Leukemia, Myeloid / pathology
-
Molecular Sequence Data
-
Myeloid-Lymphoid Leukemia Protein / genetics*
-
Nucleic Acid Hybridization
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
RNA-Binding Proteins / genetics
-
RNA-Binding Proteins / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sequence Homology, Nucleic Acid
-
Translocation, Genetic
-
Zinc Fingers
Substances
-
CCAAT-Enhancer-Binding Protein-beta
-
CELF1 Protein
-
CELF1 protein, human
-
KMT2A protein, human
-
RNA, Messenger
-
RNA-Binding Proteins
-
Myeloid-Lymphoid Leukemia Protein
-
Histone-Lysine N-Methyltransferase