In:
Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 1606-1606
Abstract:
numerous chromosomal translocations, all of which involve the gene encoding retinoid acid receptor a (RARa), resulting in the generation of corresponding oncogenic fusion proteins including PML-RARa and PLZF- RARa (hereafter referred as to X- RARa). However, through deregulating which downstream genetic program(s) X- RARas perturb the hematopoiesis has remained unclear. Here we report that Rig-I, a putative RNA helicase, was identified in RA-induced granulocytic differentiation of APL cell line NB4 cells. Interestingly, the up-regulation of Rig-I was also realized in RA-treated freshly isolated primary APL blasts harboring PML-RARa and HL-60 cell line, but not in RA-treated NB4 variant NB4-R2 (RA refractory) and APL blasts carrying PLZF-RARa, suggesting that the induced Rig-I activity is one essential step underlying the granulocytic differentiation of myeloid leukemia cells. In line with this, the knockout mice of Rig-I produced a phenotype of profound granulocytosis with moderate differentiation blockage; and conversely the overexpression of Rig-I inhibited in vivo hematopoietic reconstitution of transduced normal primitive bone marrow cells. Most importantly, the Rig-I expression was found significantly repressed in myeloid compartment of X-RARa transgenic mice, and that the retroviral transduction of Rig-I cDNA into murine APL blasts carrying hMRP8-PML/RARa greatly decreased their leukemogenesis reconstitution ability in sublethally-irradiated syngeneic recipients. Moreover, we found that Rig-I integrity is required for the full expression of TRAIL, whose expression is critical factor in determining the pool size of myeloid cells. Such, we characterize Rig-I as a crucial negative regulator of granulopoiesis and a potential candidate for developing molecule-based target therapy of myeloid leukemia.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V106.11.1606.1606
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2005
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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