Quantitative Comparison of BCR/ABL Transcript Levels in Bone Marrow and Peripheral Blood Specimens from Patients with Minimal Residual Disease.

Chronic Myeloid Leukemia (CML) is diagnosed by the presence of the Philadelphia chromosome (Ph⁺). The number of cells containing the bcr/abl chromosomal translocation diminishes dramatically after current standard of care treatment. Patient progress is monitored quantitatively and long-term prognosis is favorable if the Ph⁺ cells are no longer detected by cytogenetic analysis or FISH (sensitivity of 20% and 2% respectively). Molecular monitoring of cDNA BCR/ABL transcripts is widely used to assess levels of minimal residual disease (MRD). In our laboratory, quantitative RT-PCR allows detection of BCR/ABL transcript down to 1 x 10⁻⁵ or one BCR/ABL transcript in 100,000 reference gene transcripts. Serial values from bone marrow (BM) and blood specimens are tracked over time and monitored for increases that may indicate unfavorable changes in disease status. Though the literature indicates that the levels of BCR/ABL transcript in BM and blood samples are comparable at the time of diagnosis, this may not be true in patients with MRD. To explore this question we compared BCR/ABL transcript levels in paired BM and blood samples that were either collected together or separately but within a short time frame. In 36% of these cases both specimen types had detectable low-level BCR/ABL transcript. The levels of transcript in bone marrow were consistently higher than the levels in the associated blood specimen, though there was a wide range of variability (3-50 fold). Additionally, when blood levels of transcript were near the lower limit of detection, we were more likely to observe a larger difference relative to bone marrow transcript levels than when blood levels of transcript were higher. These results indicate that while both BM and blood specimens are valuable for serial molecular monitoring, they may not be equivocal when sampled from patients with MRD. If a patient has been monitored using blood specimens, periodic concurrent testing of blood and bone marrow specimens can provide clinical utility.