CORRELATION BETWEEN THE PROPORTION OF PHILADELPHIA-CHROMOSOME-POSITIVE METAPHASE CELLS AND LEVELS OF BCR-ABL MESSENGER-RNA IN CHRONIC MYELOID-LEUKEMIA

We have sought to define the relationship between the proportion of marrow metaphases showing the Philadelphia chromosome (Ph) and levels of BCR-ABL mRNA assessed by quantitative polymerase chain reaction (PCR) in patients with chronic myeloid leukaemia (CML). From a total of 141 patients, 164 PCR assays were performed on peripheral blood samples taken within 2 weeks of a bone marrow specimen analysed by cytogenetics. BCR-ABL mRNA was quantified in all 106 PCR-positive samples by competitive PCR; results ranged from < 10 to 3.4 x 10(6) transcripts/mu g RNA. Twenty-one chronic-phase patients had a median of 5.0 x 10(5) BCR-ABL transcripts/mu g RNA; no difference in levels of the fusion mRNA was found between 15 Ph-positive and six Ph-negative, BCR-ABL-positive patients. Ph-positive metaphases were not detected in any individual who was PCR negative (n = 58) and in only a single patient who was PCR positive with < 10(3) BCR-ABL transcripts/mu g RNA (n = 44). Conversely, of 41 samples from patients in haematological remission who had > 10(3) BCR-ABL transcripts/mu g RNA, 30 had at least one Ph-positive metaphase. The highest level of BCR-ABL transcripts at which Ph-positive metaphases were not detected was 1.5 x 10(4). For the 46 patients who had at least one Ph-positive metaphase, a good correlation (Spearman coefficient = 0.83, P < 0.0001) was found between the percentage of Ph-positive metaphases and BCR-ABL transcript levels. We conclude that quantitative PCR for BCR-ABL is an effective method for monitoring CML patients after bone marrow transplantation and is less invasive than conventional cytogenetic studies of bone marrow. (C) 1995 Wiley-Liss, Inc