Standardized definitions of molecular response in chronic myeloid leukemia

Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: Importance of achieving treatment‐free remission

“…MMR is defined as BCR-ABL1 IS 0.1% [24]. Molecular response 4 (MR 4 ) is defined as BCR-ABL1 IS 0.01% [11,26] and MR 4.5 is defined as BCR-ABL1 IS 0.0032% [11,26]. Specification of the required number of control transcripts in the testing sample provides a standardized method of ensuring assay sensitivity.…”

“…Specification of the required number of control transcripts in the testing sample provides a standardized method of ensuring assay sensitivity. For example, 10,000 control ABL1 transcripts are required for a determination of MR 4 and 32,000 ABL1 transcripts for MR 4.5 [11,26].…”

Technical Issues Behind Molecular Monitoring in Chronic Myeloid Leukemia

“…Through this short communication, we would like to stimulate a debate on the monitoring of chronic myeloid leukemia, a disorder that requires frequent laboratory analysis by RNA reverse transcription and realtime quantitative PCR (RQ-PCR). This is a challenging procedure influenced by a number of factors that are difficult to control [1,2], and troubled by the need to use reference materials to standardize results against the socalled international scale (IS) [3]. The residual disease is evaluated through the amount of BCR-ABL1 transcript, and a patient's response is reported in terms of IS logarithmic reductions, up to the possible condition of apparent undetectable disease [2].…”

“…This is a challenging procedure influenced by a number of factors that are difficult to control [1,2], and troubled by the need to use reference materials to standardize results against the socalled international scale (IS) [3]. The residual disease is evaluated through the amount of BCR-ABL1 transcript, and a patient's response is reported in terms of IS logarithmic reductions, up to the possible condition of apparent undetectable disease [2]. Actually, the outcome of RQ-PCR represents only an estimation of the leukemic clone based on the assumed proportionality between chimeric RNA and leukemic cells.…”

“…Even positive (but barely detectable) results are difficult to interpret because of the intrinsic variability of gene expression: patients with few leukemic cells can give significantly different results, depending on small variations in the mutual transcription levels of BCR-ABL1 and the reference gene used as a normalizer (usually ABL1, BCR, or GUSB [1]). As a consequence, a clear definition of molecular response is still under elaboration, though the potential for drug discontinuation makes this subject a pressing issue [2]. A survey conducted by the College of American Pathologists pointed out that diverse laboratories testing the same sample obtained different results [1].…”