Genomic imbalances in T-cell acute lymphoblastic leukemia cell lines.
Genomic imbalances were investigated in 15 T-cell acute lymphoblastic leukemia cell lines using the comparative genomic hybridization (CGH) technique. In addition, in vitro response to the cytostatic drug doxorubicin was evaluated by means of a growth inhibition assay. The number of significant DNA copy number alterations (CNAs) varied from 0 to 16 per cell line and the number of additional alterations with borderline significance was in a range of 0-7. Three of the cell lines had a total number of genomic changes of >/=20, five had 11-19, and eight had </=10 CNAs. One cell line did not show any imbalance at all. Among the significant CNAs, losses of genomic material were slightly more frequent than gains (60:49). Gains dominated among the borderline alterations compared to losses (45:9). CNAs common to all cell lines examined were not found. The most frequent genomic imbalance (gain of 6q23) was shared by 9 of the 15 cell lines. A significant loss of 18q23 was observed in eight lines, however, often close to borderline significance. Seven of the cell lines were characterized by a loss of the entire short arm of chromosome 9 or parts of it with 9p21 as minimal band of overlap. Interestingly, cell lines with a 9p21 deletion exhibited twice the number of gains and 1.6 times the number of losses per line as compared with the cell lines without this deletion. A consistent pattern of the CNAs accompanying the 9p deletion could not be detected, although some associations were more obvious than others, e.g., gains of 6q22 in five cell lines with del(9p21), of 6p21 in four lines combined with a gain of 6q22, and of 20q in four cell lines, of 1p32 in three of these seven lines, a loss of 14q32 in three of them. Three of the lines with 9p deletion had gains of 6p21, 6q22 and 20q in common. Enh(6q22) or dim(14q32), respectively, were found in only one of the nine cell lines without the 9p deletion. Based on the dose response curves of the cell lines for doxorubicin, eight doxorubicin-sensitive cell lines had an inhibition concentration 50% (IC50) <10 nM (CCRF-CEM2, JURKAT, KE-37, MOLT-3, MOLT-4, P12-Ichikawa, PEER, and RPMI-8402) and seven doxorubicin-resistant cell lines had an IC50 >10 nM (BE-13, CCRF-CEM1, HUT-78, J-Jhan, Karpas-45, MOLT-17, and PF-382). The average number of CNAs per cell line was higher in the sensitive than in the resistant group (total 13.1:8.5; significant CNAs 9.1:5.8).
Gebhart
Erich
E
Institute for Human Genetics, University of Erlangen-Nurnberg, D-91054 Erlangen, Germany. egebhart@humgenet.uni-erlangen.de
Thoma
Karen
K
Verdorfer
Irmgard
I
Drexler
Hans Gunther
HG
Efferth
Thomas
T
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004317:Doxorubicin