Alitalo K, Saksela K, Winqvist R, Alitalo R, Keski-Oja J, Laiho M, Ilvonen M, Knuutila S, de la Chapelle A
Lancet. 1985 Nov 9;2(8463):1035-9. doi: 10.1016/s0140-6736(85)90907-9.
Cytogenetic analysis of bone-marrow cells from a woman with preleukaemia showed numerous mitoses with trisomy 4 and double minute chromosomes. These abnormalities were later seen in blood cells during subsequent acute myeloid leukaemia (AML). Complete remission was achieved with three courses of doxorubicin, cytosine arabinoside, and prednisone. A further clonal abnormality, trisomy 6, was seen in leukaemic cells after the first relapse. Analyses of total DNA from the peripheral-blood cells during relapse showed that the c-myc oncogene was amplified about 30-fold in the leukaemic cells. The N-myc, c-mos, and c-myb oncogenes showed only single-copy signals. On average about two copies of c-myc resided on each dmin chromosome. The finding of amplification of a cellular oncogene (c-myc) in fresh AML cells containing double minute chromosomes suggests that clonal evolution of some leukaemia cell populations may involve selection for increased dosage of oncogenes.
