Imatinib mesylate was designed as an inhibitor targeting the BCR-ABL tyrosine 
kinase, the molecular counterpart of the Philadelphia translocation 
t(9;22)(q34;q11). We report on a patient with chronic myeloid leukemia (CML) 
undergoing acceleration during imatinib treatment. Cytogenetic analysis revealed 
four different cell populations: 
46,XX,t(9;22)(q34;q11),der(18)t(2;18)(p11;p11)[1]/47,idem,i(17)(q10),-der(18)t(2;18),+der(22)t(9;22)[1]/46,idem,-t(9;22),der(9)t(9;22),ider(22)t(9;22)[12]/ 
47,idem,-t(9;22),der(9)t(9;22),+22,ider(22)t(9;22)x2[1]. FISH analysis confirmed 
the presence of these four clones. Moreover, 49% of the interphase nuclei 
contained either one or two clustered fusion signals, indicating a low-level 
amplification of the BCR-ABL fusion gene. With quantitative real-time RT-PCR, a 
BCR-ABL/G6PDH ratio of 0.8 was determined, which is comparable to that measured 
in the K562 cell line with a known BCR-ABL amplification and which is increased 
by more than about 60-fold compared to a CML at diagnosis with >80% 
Philadelphia-positive cells. We give further evidence that the genomic BCR-ABL 
amplification results in an increased level of BCR-ABL transcript linking two 
potent mechanisms of resistance against imatinib treatment.