Establishment and cytogenetic characterization of a human acute lymphoblastic leukemia cell line (ALL-VG) with ETV6/ABL1 rearrangement.
Fusion kinases (FK) like BCR/ABL1 mediate leukemic transformation and represent therapeutic targets. Fusion of ETV6 (ETS translocation variant 6, previously known as TEL) to ABL1 due to t(9;12) has been observed in various hematological malignancies. ETV6/ABL1 and BCR/ABL1 FK display similar activity but they may not be identical in function. Here we present the generation of an ETV6/ABL1 positive human acute lymphoblastic leukemia (ALL) cell line, ALL-VG. The cell line expressed ETV6/ABL1 fusion transcripts and displayed sensitivity to imatinib with an IC(50) of 0.1 microM. Karyotyping did not reveal overt t(9;12), suggesting a cryptic translocation. Fluorescent in situ hybridization and array-based comparative genomic hybridization were performed to characterize the rearrangement. ETV6/ABL1 fusion was demonstrated to result from insertion of a duplicated 300 to 1300 kb region of 9q34 that contained the distal portion of the ABL1 gene, into the ETV6 locus on 12p13. With this insertion, an 1150 to 1750 kb region of 12p13 that contained the distal portion of the ETV6 gene as well the cyclin dependent kinase inhibitor (CDKN) 1B gene was lost. Furthermore, the cells displayed a del(9)(p21.1 approximately p23), typically associated with loss of CDKN2A and CDKN2B. The ALL-VG cell line may serve as a tool for the study of ETV6/ABL1.
Baeumler
Joerg
J
Department of Hematology, JW Goethe University, Frankfurt am Main, Germany.
Szuhai
Karoly
K
Falkenburg
J H Frederik
JH
van Schie
Marianke L J
ML
Ottmann
Oliver G
OG
Nijmeijer
Bart A
BA
D000328:Adult; D001549:Benzamides; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D002896:Chromosomes, Human, Pair 6; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012074:Remission Induction; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases