WT1 gene expression lowered by IL-12 In vitro in peripheral blood mononuclear cells from patients with leukemia or myelodysplastic syndromes.
- Author:
Ling PAN
1
;
Xue-Jun ZHANG
;
Zhi-Yun NIU
;
Xiao-Hui SUO
;
Jing-Yu ZHANG
;
Lin YANG
;
Xiao-Jun LIU
;
Shu-Kai QIAO
;
Zuo-Ren DONG
;
Ruzo OHNO
Author Information
1. Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. lingpan2000@yahoo.com
- Publication Type:Journal Article
- MeSH:
Adult;
Aged;
Aged, 80 and over;
Female;
Humans;
Interleukin-12;
pharmacology;
Leukemia, Myeloid, Acute;
genetics;
metabolism;
Leukocytes, Mononuclear;
metabolism;
Male;
Middle Aged;
Myelodysplastic Syndromes;
genetics;
metabolism;
Neoplasm, Residual;
genetics;
metabolism;
RNA, Messenger;
biosynthesis;
genetics;
WT1 Proteins;
biosynthesis;
genetics
- From:
Journal of Experimental Hematology
2006;14(3):501-507
- CountryChina
- Language:English
-
Abstract:
Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6 CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.
