Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia
- PMID: 7651838
- PMCID: PMC307102
- DOI: 10.1093/nar/23.14.2762
Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia
Abstract
We previously isolated the AML1 gene, which is rearranged by the t(8;21) translocation in acute myeloid leukemia. The AML1 gene is highly homologous to the Drosophila segmentation gene runt and the mouse transcription factor PEBP2 alpha subunit gene. This region of homology, called the Runt domain, is responsible for DNA-binding and protein--protein interaction. In this study, we isolated and characterized various forms of AML1 cDNAs which reflect a complex pattern of mRNA species. Analysis of these cDNAs has led to the identification of two distinct AML1 proteins, designated AML1b (453 amino acids) and AML1c (480 amino acids), which differ markedly from the previously reported AML1a (250 amino acids) with regard to their C-terminal regions, although all three contain the Runt domain. The large C-terminal region common to AML1b and AML1c is suggested to be a transcriptional activation domain. AML1c differs from AML1b by only 32 amino acids in the N-terminal. Characterization of the genomic structure revealed that the AML1 gene consists of nine exons and spans > 150 kb of genomic DNA. Northern blot analysis demonstrated the presence of six major transcripts, encoding AML1b or AML1c, which can all be explained by the existence of two promoters, alternative splicing and differential usage of three polyadenylation sites. A minor transcript encoding AML1a which results from alternative splicing of a separate exon can be detected only by reverse transcription-polymerase chain reaction amplification. The distinct proteins encoded by the AML1 gene may have different functions, which could contribute to regulating cell growth and/or differentiation through transcriptional regulation of a specific subset of target genes.
Similar articles
-
The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias.Haematologica. 1997 May-Jun;82(3):364-70. Haematologica. 1997. PMID: 9234595 Review.
-
An acute myeloid leukemia gene, AML1, regulates transcriptional activation and hemopoietic myeloid cell differentiation antagonistically by two alternative spliced forms.Leukemia. 1997 Apr;11 Suppl 3:299-302. Leukemia. 1997. PMID: 9209372
-
Leukemogenesis by the chromosomal translocations.Leukemia. 1997 Apr;11 Suppl 3:294-6. Leukemia. 1997. PMID: 9209370 Review.
-
Overexpression of the AML1 proto-oncoprotein in NIH3T3 cells leads to neoplastic transformation depending on the DNA-binding and transactivational potencies.Oncogene. 1996 Feb 15;12(4):883-92. Oncogene. 1996. PMID: 8632911
-
AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular heterogeneity and usage of splicing sites frequently involved in the generation of normal AML1 transcripts.Genes Chromosomes Cancer. 1994 Dec;11(4):226-36. doi: 10.1002/gcc.2870110405. Genes Chromosomes Cancer. 1994. PMID: 7533526
Cited by
-
Age-related promoter-switch regulates Runx1 expression in adult rat hearts.BMC Cardiovasc Disord. 2023 Nov 7;23(1):541. doi: 10.1186/s12872-023-03583-3. BMC Cardiovasc Disord. 2023. PMID: 37936072 Free PMC article.
-
RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome.Hum Genomics. 2023 Sep 5;17(1):83. doi: 10.1186/s40246-023-00531-2. Hum Genomics. 2023. PMID: 37670378 Free PMC article. Review.
-
The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21).Cells. 2023 Jan 18;12(3):357. doi: 10.3390/cells12030357. Cells. 2023. PMID: 36766699 Free PMC article. Review.
-
Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling.Hepatology. 2023 Jun 1;77(6):1866-1881. doi: 10.1097/HEP.0000000000000041. Epub 2023 Jan 3. Hepatology. 2023. PMID: 36647589 Free PMC article.
-
A comprehensive landscape of transcription profiles and data resources for human leukemia.Blood Adv. 2023 Jul 25;7(14):3435-3449. doi: 10.1182/bloodadvances.2022008410. Blood Adv. 2023. PMID: 36595475 Free PMC article.
References
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases