Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.
The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.
Wada
H
H
Department of Virology, National Children's Medical Research Center, Tokyo, Japan.
Mizutani
S
S
Nishimura
J
J
Usuki
Y
Y
Kohsaki
M
M
Komai
M
M
Kaneko
H
H
Sakamoto
S
S
Delia
D
D
Kanamaru
A
A
D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex / Q000378:metabolism; D000954:Antigens, Surface / Q000032:analysis; D001483:Base Sequence; D015139:Blotting, Southern; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D005091:Exons; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics*; D015321:Gene Rearrangement; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010770:Phosphotransferases / Q000378:metabolism; D011233:Precipitin Tests; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D010770:Phosphotransferases; D016044:Fusion Proteins, bcr-abl