Abstract
Antisense oligonucleotides were used to determine the role of the BCR-ABL gene in the proliferation of chronic myeloid leukaemia (CML) clonogenic cells. Peripheral blood Philadelphia chromosome positive cells were obtained from eight CML patients at diagnosis (chronic phase = 7; accelerated phase = 1). Mononuclear cells were incubated with synthetic antisense 18-mer oligonucleotides complementary to the two different junctions b2a2 or b3a2. The type of junction (b2a2 or b3a2) was previously determined by RT-PCR techniques. Cells incubated for 12 to 14 hours with or without sense oligonucleotides served as controls. After incubation with oligonucleotides, the cell DNA synthesis was analysed by flow cytometry using the BrdUrd/DNA method and the cell plating efficiency in methylcellulose was determined. In six of the seven patients in chronic phase, there was a significant inhibition of CFU-GM production which was only 68.4 +/- 19%; (p < .01) of that found in controls. The S phase index, which depends upon the percentage of S phase cells as well as the fluorescence intensity, was 48 +/- 29% (p < .01) of the control values for the seven patients in chronic phase. Interestingly, for the only CML patient in accelerated phase, antisen...Continue Reading
References
Jan 1, 1992·Cytometry·F LacombeJ Reiffers
Sep 18, 1992·Cell·C L SawyersO N Witte
Mar 1, 1991·British Journal of Haematology·J ReiffersF Lacombe
Aug 2, 1991·Science·C SzczylikB Calabretta
Jun 1, 1991·The Journal of Clinical Investigation·H AhujaM Cline
Feb 16, 1990·Science·G Q DaleyD Baltimore
Mar 2, 1990·Science·T G LugoO N Witte
Aug 25, 1989·Cell·R A Van EttenD Baltimore
Sep 8, 1989·Science·D CaraccioloB Calabretta
Jun 13, 1985·Nature·E ShtivelmanE Canaani
May 1, 1988·Cytometry·F LacombeM R Boisseau
Jan 23, 1986·The New England Journal of Medicine·J M GoldmanJ Hows
Jan 1, 1984·Cell·J GroffenG Grosveld
Feb 27, 1993·Lancet·F X MahonJ Reiffers
Sep 4, 1993·Lancet·M A KirklandJ M Goldman
Jul 1, 1993·The Journal of Clinical Investigation·T SkorskiB Calabretta
Jan 1, 1990·Leukemia & Lymphoma·J M Goldman