title: Inhibition of small GTPase RalA regulates growth and arsenic-induced apoptosis in chronic myeloid leukemia (CML) cells.
abstract: Chronic myelogenous leukemia (CML) results from the transformation of a primitive hematopoietic cell by the bcr-abl gene. RalA, one of the Ras superfamily of small GTPases, is a downstream molecule of bcr-abl fusion protein in ras signaling pathway, but its role in CML is poorly understood. Here, we first detected RalA level in CML cells, which is highly expressed and distributed mainly in the cytoplasm and/or partially in endomembrane. Next, siRNA was used to deplete RalA expression for elucidating its function. The results showed that siRNA RalA effectively inhibited cell viability, induced apoptosis and enhanced sensitivity of arsenic trioxide (ATO), and there are some synergistic effects of anti-CML between RalA siRNA and ATO. Finally, we found that ATO also could downregulate protein level of bcr-abl in K562 and KCL-22. Our research provides evidence that RalA might also serve as linchpin modulators in leukemia, and combinatorial therapies of dual inhibition of bcr-abl and ras signaling pathways have a great potential in treatment of CML.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Yumin
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaochuang
authors.initials: X
authors.lastname: Luo
authors.forename: Jia
authors.initials: J
authors.lastname: Fei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020725:ral GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D034741:RNA, Small Interfering; D016044:Fusion Proteins, bcr-abl; C492198:RALA protein, human; D020725:ral GTP-Binding Proteins; D000077237:Arsenic Trioxide