Abstract
The expression of the PML gene was investigated in purified early hematopietic 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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3529-3540 |
| Number of pages | 12 |
| Journal | Oncogene |
| Volume | 18 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Jun 10 1999 |
Fingerprint
Keywords
- Erythropoiesis
- HPCs
- PML
- RB
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Expression and role of PML, gene in normal adult hematopoiesis : Functional interaction between PML and Rb proteins in erythropoiesis. / Labbaye, C.; Valtieri, M.; Grignani, F.; Puglisi, R.; Luchetti, L.; Masella, B.; Alcalay, M.; Testa, U.; Peschle, C.
In: Oncogene, Vol. 18, No. 23, 10.06.1999, p. 3529-3540.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression and role of PML, gene in normal adult hematopoiesis
T2 - Functional interaction between PML and Rb proteins in erythropoiesis
AU - Labbaye, C.
AU - Valtieri, M.
AU - Grignani, F.
AU - Puglisi, R.
AU - Luchetti, L.
AU - Masella, B.
AU - Alcalay, M.
AU - Testa, U.
AU - Peschle, C.
PY - 1999/6/10
Y1 - 1999/6/10
N2 - The expression of the PML gene was investigated in purified early hematopietic 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 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.
AB - The expression of the PML gene was investigated in purified early hematopietic 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 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.
KW - Erythropoiesis
KW - HPCs
KW - PML
KW - RB
UR - http://www.scopus.com/inward/record.url?scp=0033542424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033542424&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1202682
DO - 10.1038/sj.onc.1202682
M3 - Article
C2 - 10376531
AN - SCOPUS:0033542424
VL - 18
SP - 3529
EP - 3540
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 23
ER -