Correlation between the proportion of Philadelphia chromosome‐positive metaphase cells and levels of BCR‐ABL mRNA in chronic myeloid leukaemia

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Abstract
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 × 106 transcripts/μg RNA. Twenty-one chronic-phase patients had a median of 5.0 × 105 BCR-ABL transcripts/μg 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 < 103 BCR-ABL transcripts/μg RNA (n = 44). Conversely, of 41 samples from patients in haematological remission who had >103 BCR-ABL transcripts/μg 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 × 104. For the 46 patients who had at least one Ph-positive metaphase, a good correlation (Spearman coefficient = 0.83, P 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.