Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

Jones, L., Wei, G., Sevcikova, S., Phan, V., Jain, S., Shieh, A., Wong, J. C., Li, M., Dubansky, J., Maunakea, M. L., Ochoa, R., Zhu, G., Tennant, T. R., Shannon, K. M., Lowe, S. W., Le Beau, M. M., Kogan, S. C. (2010) Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia. J Exp Med, 207 (12). pp. 2581-94. ISSN 0022-1007

[img]
Preview
PDF (Paper)
Lowe J Exp Med 2010.pdf - Published Version

Download (2371Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/21059853
DOI: 10.1084/jem.20091071

Abstract

Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia (AML). It has been hypothesized that gain of the MYC protooncogene is of central importance in trisomy 8, but the experimental data to support this are limited and controversial. In a mouse model of promyelocytic leukemia in which the MRP8 promoter drives expression of the PML-RARA fusion gene in myeloid cells, a Myc allele is gained in approximately two-thirds of cases as a result of trisomy for mouse chromosome 15. We used this model to test the idea that MYC underlies acquisition of trisomy in AML. We used a retroviral vector to drive expression of wild-type, hypermorphic, or hypomorphic MYC in bone marrow that expressed the PML-RARA transgene. MYC retroviruses cooperated in myeloid leukemogenesis and suppressed gain of chromosome 15. When the PML-RARA transgene was expressed in a Myc haploinsufficient background, we observed selection for increased copies of the wild-type Myc allele concomitant with leukemic transformation. In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML.

Item Type: Paper
Uncontrolled Keywords: Animals Cells, Cultured *Chromosomes, Human, Pair 8 Disease Models, Animal *Genes, myc Humans Leukemia, Promyelocytic, Acute/etiology/*genetics Mice Oncogene Proteins, Fusion/genetics Recurrence *Trisomy
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome

diseases & disorders > cancer > cancer types > leukemia
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL labs > Lowe lab
Depositing User: Matt Covey
Date Deposited: 14 Oct 2015 17:09
Last Modified: 06 Nov 2017 20:21
PMCID: PMC2989761
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31920

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving