Abstract
The expression of the PML gene was investigated in purified early hematopoietic progenitor cells (HPCs) induced to unilineage erythroid or granulocytic differentiation. PML mRNA and protein, while barely detectable in quiescent HPCs, are consistently induced by growth factor stimulation through the erythroid or granulocytic lineage. Thereafter, PML is downmodulated in late granulocytic maturation, whereas it is sustainably expressed through the erythroid pathway. In functional studies, PML expression was inhibited by addition of antisense oligomers targeting PML mRNA (α-PML). Interestingly, early treatment (day 0 HPCs) with α-PML reduced the number of both erythroid and granulocytic colonies, whereas late treatment (day 5 culture) reduced erythroid, but not granulocytic, clonogenesis. These findings suggest that PML is required for early hematopoiesis and erythroid, but not granulocytic maturation. The pattern of PML expression in normal hematopoiesis mimics that of retinoblastoma pRb 105. Combined treatment of HPCs with α-PML and α-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development. Furthermore, PML and pRb 105 were co-immunoprecipitated in cellular lysates derived from erythroid precursors indicating that this functional interaction may have a biochemical basis. These results suggest a key functional role of PML in early hematopoiesis and late erythropoiesis: the latter phenomenon may be related to the molecular and functional interaction of PML with pRb 105.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ahn JH and Hayward GS. . 1997 J. Virol. 71: 4599–4613.
Ahn JH, Brignale III EJ and Hayward GS. . 1998 Mol. Cell. Biol. 18: 4899–4913.
Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M, Helin K and Pelicci PG. . 1998 Mol. Cell. Biol. 18: 1084–1093.
Alcalay M, Zangrilli D, Fagioli M, Pandolfi PP, Mencarelli A, Lo Coco F, Biondi A, Grignani F and Pelicci PG. . 1992 Proc. Natl. Acad. Sci. USA 89: 4840–4844.
Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E and Freemont PS. . 1995 EMBO J. 14: 1532–1541
Borden KL, Lally JM, Martin SR, O'Reilly NJ, Solomon E and Freemont PS. . 1996 Proc. Natl. Acad. Sci. USA 93: 1601–1606.
Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S and Bishop JM. . 1997 Proc. Natl. Acad. Sci. USA 94: 2551–2556.
Caré A, Testa U, Bassani A, Tritarelli E, Montesoro E, Samoggia P, Cianetti L and Peschle C. . 1994 Mol. Cell. Biol. 14: 4872–4877.
Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P and Degos L. . 1990 Blood 76: 1704–1709.
Chang KS, Fan YH, Andreeff M, Liu J and Mu ZM. . 1995 Blood 85: 3646–3653.
Chen PL, Riley DJ, Chen Y and Lee WH. . 1996a Genes Dev. 10: 2794–2804.
Chen PL, Riley DJ, Chen-Kiang S and Lee WH. . 1996b Proc. Natl. Acad. Sci. USA 93: 465–469.
Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S and Zelent A. . 1993 EMBO J. 12: 1161–1167.
Condorelli G, Testa U, Valtieri M, Vitelli L, De Luca A, Barberi T, Montesoro E, Campisi S, Giordano A and Peschle C. . 1995 Proc. Natl. Acad. Sci. USA 92: 4808–4812.
Daniel MT, Koken M, Romagne O, Barbey S, Bazarbachi A, Stadler M, Guillemin MC, Degos L, Chomienne C and de Thé H. . 1993 Blood 82: 1858–1867.
de Thé H, Lavau C, Marchio A, Chomienne C, Degos L and Dejean A. . 1991 Cell 66: 675–684.
Doucas V, Ishov AM, Romo A, Juguilon H, Weitzman MD, Evans RM and Maul GG. . 1996 Genes Dev. 10: 196–207.
Dyck JA, Maul GG, Miller Jr WH, Chen JD, Kakizuka A and Evans RM. . 1994 Cell 76: 333–343.
Everett RD and Maul GG. . 1994 EMBO J. 13: 5062–5069.
Everett RD, Meredith M, Orr A, Cross A, Kathoria M and Parkinson J. . 1997 EMBO J. 16: 1519–1530.
Fagioli M, Alcalay M, Pandolfi PP, Venturini L, Mencarelli A, Simeone A, Acampora D, Grignani F and Pelicci PG. . 1992 Oncogene 7: 1083–1091.
Flenghi L, Fagioli M, Tomassoni L, Pileri S, Gambacorta M, Pacini R, Grignani F, Casini T, Ferrucci PF, Martelli MF, Pelicci PG and Falini B. . 1995 Blood 85: 1871–1880.
Gabbianelli M, Sargiacomo M, Pelosi E, Testa U, Isacchi G and Peschle C. . 1990 Science 249: 1561–1564.
Giampaolo A, Sterpetti P, Bulgarini D, Samoggia P, Pelosi E, Valtieri M and Peschle C. . 1994 Blood 84: 3637–3647.
Goddard AD, Borrow J, Freemont PS and Solomon E. . 1991 Science 254: 1371–1374.
Grignani F, Fagioli M, Alcalay M, Longo L, Pandolfi PP, Donti E, Biondi A, Lo Coco F, Grignani F and Pelicci PG. . 1994 Blood 83: 10–25.
Grignani F, Ferrucci PF, Testa U, Talamo G, Fagioli M, Alcalay M, Mencarelli A, Grignani F, Peschle C, Nicoletti I and Pelicci PG. . 1993 Cell 74: 423–431.
Grignani F, Testa U, Fagioli M, Barberi T, Masciulli R, Mariani G, Peschle C and Pelicci PG. . 1995 Cancer Res. 55: 440–443.
Grignani F, Testa U, Rogaia D, Ferrucci PF, Samoggia P, Pinto A, Aldinucci D, Gelmetti V, Fagioli M, Alcalay M, Seeler J, Grignani F, Nicoletti I, Peschle C and Pelicci PG. . 1996 EMBO J. 15: 4949–4958.
Grisolano JL, Wesselschmidt RL, Pelicci PG and Ley TJ. . 1997 Blood 89: 376–387.
Guiochon-Mantel A, Savouret JF, Quignon F, Delabre K, Milgrom E and De Thé H. . 1995 Mol. Endocrinol. 9: 1791–1803.
He D, Mu ZM, Le X, Hsieh JT, Pong RC, Chung LW and Chang KS. . 1997a Cancer Res. 57: 1868–1872.
He LZ, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, Cattoretti G and Pandolfi PP. . 1997b Proc. Natl. Acad. Sci. USA 94: 5302–5307.
Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ and Wang ZY. . 1988 Blood 72: 567–572.
Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, Lanotte M, Berger R and Chambon P. . 1992 EMBO J. 11: 629–642.
Koken MH, Puvion-Dutilleul F, Guillemin MC, Viron A, Linares-Cruz G, Stuurman N, de Jong L, Szostecki C, Calvo F, Chomienne C, Degos L, Puvion E and deThé H. . 1994 EMBO J. 13: 1073–1083.
Labbaye C, Valtieri M, Barberi T, Meccia E, Masella B, Pelosi E, Condorelli GL, Testa U and Peschle C. . 1995 J. Clin. Invest. 95: 2346–2358.
Labbaye C, Valtieri M, Testa U, Giampaolo A, Meccia E, Sterpetti P, Parolini I, Pelosi E, Bulgarini D, Cayre YE and Peschle C. . 1994 Blood 83: 651–656.
Liu JH, Mu ZM and Chang KS. . 1995 J. Exp. Med. 181: 1965–1973.
Mu ZM, Chin KV, Liu JH, Lozano G and Chang KS. . 1994 Mol. Cell. Biol. 14: 6858–6867.
Nason-Burchenal K, Gandini D, Botto M, Allopenna J, Seale JR, Cross NC, Goldman JM, Dmitrovsky E and Pandolfi PP. . 1996 Blood 88: 3926–3936.
Nevins JR. . 1992 Science 258: 424–429.
Perez A, Kastner P, Sethi S, Lutz Y, Reibel C and Chambon P. . 1993 EMBO J. 12: 3171–3182.
Rabbitts TH. . 1991 Cell 67: 641–644.
Reddy BA, Etkin LD and Freemont PS. . 1992 Trends Biochem. Sci. 17: 344–345.
Redner RL, Rush EA, Faas S, Rudert WA and Corey SJ. . 1996 Blood 87: 882–886.
Rousselot P, Hardas B, Patel A, Guidez F, Gaken J, Castaigne S, Dejean A, de Thé H, Degos L and Farzaneh F. . 1994 Oncogene 9: 545–551.
Sawyers CL, Denny CT and Witte ON. . 1991 Cell 64: 337–350.
Shivdasani RA and Orkin SH. . 1996 Blood 87: 4025–4039.
Snow CM, Senior A and Gerace L. . 1987 J. Cell. Biol. 104: 1143–1156.
Taya Y. . 1997 Trends Biochem. Sci. 22: 14–17.
Valtieri M, Gabbianelli M, Pelosi E, Bassano E, Petti S, Russo G, Testa U and Peschle C. . 1989 Blood 74: 460–470.
Valtieri M, Venturelli D, Caré A, Fossati C, Pelosi E, Labbaye C, Mattia G, Gewirtz AM, Calabretta B and Peschle C. . 1991 Blood 77: 1181–1190.
Wang ZG, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C, Grosveld F and Pandolfi PP. . 1998 Science 279: 1547–1551.
Warrell Jr RP, Frankel SR, Miller Jr WH, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A, Jakubowski A, Gabrilove J, Gordon MS and Dmitrowski E. . 1991 New Engl. J. Med. 324: 1385–1393.
Warrell Jr RP, de Thé H, Wang ZY and Degos L. . 1993 New Engl. J. Med. 329: 177–189.
Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M, Lamond A and Dejean A. . 1994 Cell 76: 345–356.
Wells RA, Catzavelos C and Kamel-Reid S. . 1997 Nat. Genet. 17: 109–113.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Labbaye, C., Valtieri, M., Grignani, F. et al. Expression and role of PML gene in normal adult hematopoiesis: functional interaction between PML and Rb proteins in erythropoiesis. Oncogene 18, 3529–3540 (1999). https://doi.org/10.1038/sj.onc.1202682
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202682
Keywords
This article is cited by
-
PML: a tumor suppressor essential for neocortical development
Nature Neuroscience (2009)
-
The tumor suppressor Pml regulates cell fate in the developing neocortex
Nature Neuroscience (2009)
-
Stemming out of a new PML era?
Cell Death & Differentiation (2009)
-
New insights into the role of PML in tumour suppression
Cell Research (2008)
-
Retinoblastoma protein and the leukemia-associated PLZF transcription factor interact to repress target gene promoters
Oncogene (2008)