PML bodies, also referred to as ND10, PODs (PML oncogenic domains) and Kr bodies, vary in size from 0.3 Ám to 1.0 Ám in diameter (reviewed in Maul et al., 2000) . The average mammalian nucleus can contain between 10 to 30 of these structures. PML bodies have been found juxtaposed to other nuclear structures such as nuclear gems and Cajal bodies, the significance of this association is unknown. Neither chromatin nor RNA is found within the central core of these bodies but newly sythesized RNA is associated with their periphery (Boisvert et al., 2000). The human MHC locus on chromosome 6 has been shown to associate preferentially with PML bodies (Shiels et al., 2001).

Although the PML protein is essential for PML body formation, many other proteins localise to these structures including Sp100, SUMO1, HAUSP, Daxx and CBP (Maul et al., 2000) . SUMO-1 modification of both PML and Sp100 may regulate the dynamics of protein localisation within PML bodies. For example, although SUMO-1 modification of the PML protein is not required for nuclear body formation, the accumulation of many other PML body-associated proteins (e.g. Daxx, Sp100) within these structures does appear to require the sumolation of PML. Consistent with PML bodies playing a role in transcriptional regulation, it has been recently reported that SUMO-1 modified PML can derepress Pax3 transcriptional activity by the sequestration of Daxx in PML bodies (Lehembre et al., 2001) .

PML bodies and Disease

PML bodies are implicated in both oncogenesis and viral infection. Some individuals suffering from acute promyelocytic leukemia (APL) have a t(15,17) translocation, which results in the fusion of the PML gene with the gene encoding the retinoic acid receptor. Cells from these individuals exhibit many small and fragmented PML bodies localised to smaller domains scattered throughout the nucleoplasm. Treatment with retinoic acid results in a reformation of PML bodies and remission of leukemia in these same individuals. PML bodies are also destroyed by herpesvirus infection, due to expression of the immediate-early gene products that appear to specifically target the PML protein (e.g. IE1 of HCMV and ICP0 of HSV) (Maul et al., 1998) . In addition, several nuclear-replicating DNA viruses (e.g. herpesviruses, adenoviruses and papovaviruses) have been reported to have their parental genomes preferentially associated with PML bodies, and their initial sites of transcription and their DNA replication centres are often juxtaposed to these bodies or their remnants (reviewed in Everett, 2001) .

  • PML body image database from

  • Human cytomegalovirus (HCMV) and PML home page of Richard Caswell.

  • Angus Lamond's PML body page


    Boisvert, F.M., Hendzel, M.J. and Bazett-Jones, D.P. (2000) Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J. Cell Biol. 148(2):283-292

    Everett, R.D. (2001) DNA viruses and viral proteins that interact with PML nuclear bodies. Oncogene 20(49):7266-7273

    Lehembre F, Muller S, Pandolfi PP, and Dejean A. (2001) Regulation of Pax3 transcriptional activity by SUMO-1-modified PML. Oncogene 20(1):1-9

    Shiels C, Islam SA, Vatcheva R, Sasieni P, Sternberg MJ, Freemont PS and Sheer D. (2001) PML bodies associate specifically with the MHC gene cluster in interphase nuclei. J. Cell Sci 114(20):3705-3716

    Maul, G. G., Negorev, D., Bell, P. and Ishov, A. M. (2000). Review: properties and assembly mechanisms of ND10, PML bodies, or PODs. J. Struct. Biol. 129:278 -287.

    Maul, G.G. (1998) Nuclear domain 10, the site of DNA virus transcription and replication. Bioessays. 20(8):660-667

    Spector, D.L. (2001) Nuclear domains. J. Cell Sci. 114 (16):2891-2893