Open AccessDigital PCR for BCR‐ABL1 Quantification in CML: Current Applications in Clinical Practice
Author(s) -
Kockerols Camille C.B.,
Valk Peter J.M.,
Levin MarkDavid,
Pallisgaard Niels,
Cornelissen Jan J.,
Westerweel Peter E.
Publication year - 2020
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/hs9.0000000000000496
Subject(s) - discontinuation , digital polymerase chain reaction , minimal residual disease , oncology , medicine , myeloid leukemia , breakpoint cluster region , clinical practice , real time polymerase chain reaction , leukemia , biology , polymerase chain reaction , genetics , receptor , gene , family medicine
Molecular monitoring of the BCR‐ABL1 transcript for patients with chronic phase chronic myeloid leukemia (CML) has become increasingly demanding. Real‐time quantitative PCR (qPCR) is the routinely used method, but has limitations in quantification accuracy due to its inherent technical variation. Treatment recommendations rely on specific BCR‐ABL1 values set at timed response milestones, making precise measurement of BCR‐ABL1 a requisite. Furthermore, the sensitivity of qPCR may be insufficient to reliably quantify low levels of residual BCR‐ABL1 in patients in deep molecular response (DMR) who could qualify for an attempt to discontinue Tyrosine Kinase Inhibitor (TKI) therapy. We reviewed the current use of digital PCR (dPCR) as a promising alternative for response monitoring in CML. dPCR offers an absolute BCR‐ABL1 quantification at various disease levels with remarkable precision and a clinical sensitivity reaching down to at least MR5.0. Moreover, dPCR has been validated in multiple studies as prognostic marker for successful TKI treatment discontinuation, while this could not be achieved using classical qPCR. dPCR may thus prospectively be the preferred method to reliably identify patients achieving treatment milestones after initiation of TKI therapy as well as for the selection and timing for TKI discontinuation.