Comparative cytogenetic analysis between cyclophosphamide-sensitive and -resistant lines of acute myeloid leukemia in the Lewis Brown Norway hybrid rat.
An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F1 hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY-resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY-sensitive and CY-resistant LBN AML lines. The CY-sensitive LBN AML cultures contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 41,XX,-1,-2,-9,del(12),del(20)(q13) + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11). The recently developed CY-resistant AML cells contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(3)(q36q42.1),del(4) (q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY-resistant line I [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent.
Kearns
W
W
Kennedy Institute, Baltimore, MD 21205.
Koelling
T
T
Yeager
A
A
D000208:Acute Disease; D000818:Animals; D002871:Chromosome Banding; D003520:Cyclophosphamide / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D014407:Tumor Cells, Cultured
D003520:Cyclophosphamide