PNAS-2: a novel gene probably participating in leukemogenesis.
OBJECTIVE
As(4)S(4) is an effective drug for the treatment of acute promyelocytic leukemia but its mechanism of action remains largely unknown. In a previous study, we identified PNAS-2, a human apoptosis-related protein gene, using gene expression profiling. In this study, we tried to clarify the role of PNAS-2 in apoptosis and leukemogenesis.


METHODS
NB4 and U937 leukemia cell lines and serial clinical samples were studied. RNA interference (RNAi) and RNA overexpression were used to address the potential role of PNAS-2 in apoptosis. PNAS-2 expression was examined using Northern blot in multiple tissues, and real-time PCR was applied to analyze PNAS-2 expression in various patient samples.


RESULTS
Functional analyses of PNAS-2 by RNAi and RNA overexpression indicate PNAS-2 is an anti-apoptosis gene. PNAS-2 expression is significantly increased in de novo or relapsed acute leukemia, but in patients in complete remission PNAS-2 levels decrease to levels comparable to those found in normal controls. In carcinomas, PNAS-2 expression was not upregulated, indicating that PNAS-2 overexpression was specific for leukemia.


CONCLUSIONS
Based on the preliminary data, we suggest that the PNAS-2 gene functions as an anti-apoptotic gene and probably participates in leukemogenesis.
Wang
Hai-Rong
HR
Department of Hematology, Ren-Ji Hospital and Shanghai Institute of Hematology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
Gu
Chun-Hong
CH
Zhu
Jian-Yi
JY
Han
Jie-Yin
JY
Zhong
Hua
H
Chen
Fang-Yuan
FY
Ouyang
Ren-Rong
RR
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D015854:Up-Regulation; D056827:Endosomal Sorting Complexes Required for Transport
D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; C499838:CHMP5 protein, human; D056827:Endosomal Sorting Complexes Required for Transport