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P190 BCR-ABL MRNA Is Expressed At Low Levels In P210-positive Chronic Myeloid And Acute Lymphoblastic Leukemias

F van Rhee, A Hochhaus, F Lin, JV Melo, JM Goldman, NC Cross

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One hundred and forty-three patients with p210 BCR-ABL-positive leukemia were studied for coexpression of p190 BCR-ABL mRNA. p190 mRNA was detected in 14 of 16 (88%) patients with chronic-phase chronic myeloid leukemia (CML) at diagnosis, in 10 of 10 (100%) CML patients in blast crisis, in 75 of 107 (70%) CML patients receiving interferon- alpha (IFN-alpha), and 10 of 10 (100%) patients with p210 BCR-ABL- positive acute lymphoblastic leukemia (ALL). Neither p210 nor p190 BCR- ABL transcripts were detected in normal healthy adults (n = 20). The numbers of p190 transcripts determined by competitive PCR in patients with CML were low compared with the numbers of p210 transcripts. The median numbers of p210 and p190 transcripts per unit volume of cDNA in positive samples were 1.0 x 10(5) (range, 15 to 1.4 x 10(6)) and 10 (range, 10 to 2.9 x 10(3)), respectively. The numbers of p190 and p210 transcripts were significantly correlated in individual samples (r = .65, P < .001). The median number of p210 BCR-ABL transcripts was significantly lower in samples negative for p190 BCR-ABL transcripts than in samples in which p190 BCR-ABL transcripts were identified (3.1 x 10(3)[n = 73] v 1.0 x 10(5)[n = 115]; P < .0001). The median ratio of p190 to p210 BCR-ABL mRNA was not significantly different between chronic phase CML (1.9 x 10(-4)) and CML in blast crisis (1.7 x 10(- 4)). The median ratio in p210 ALL was also low (1.9 x 10(-3)) but significantly higher than that of CML. We conclude that pl90 BCR-ABL transcripts are frequently present at a low level in p210 BCR-ABL- positive leukemias. p190 mRNA may arise through alternative or missplicing and its presence is probably of no pathogenetic significance.