TY - JOUR
T1 - Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest
AU - Nachmias, Boaz
AU - Krichevsky, Svetlana
AU - Gatt, Moshe E.
AU - Gross Even-Zohar, Noa
AU - Shaulov, Adir
AU - Haran, Arnon
AU - Aumann, Shlomzion
AU - Vainstein, Vladimir
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/11/10
Y1 - 2023/11/10
N2 - Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with clear prognostic and clinical implications. The monitoring of other identified mutations lacks standardization, limiting its use and incorporation in clinical trials. To overcome this problem, we designed a plasmid bearing both the sequence of the mutation of interest and the ABL reference gene. This allows the use of commercial standards for ABL to determine the MRD response in copy number. We provide technical aspects of this approach as well as our experience with 19 patients with atypical NPM1, RUNX1 and IDH1/2 mutations. In all cases, we demonstrate a correlation between response and copy number. We further demonstrate how copy number monitoring can modulate the clinical management. Taken together, we provide proof of concept of a novel yet simple tool, which allows in-house MRD monitoring for identified mutations, with ABL-based commercial standards. This approach would facilitate large multi-center studies assessing the clinical relevance of selected MRD monitoring.
AB - Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with clear prognostic and clinical implications. The monitoring of other identified mutations lacks standardization, limiting its use and incorporation in clinical trials. To overcome this problem, we designed a plasmid bearing both the sequence of the mutation of interest and the ABL reference gene. This allows the use of commercial standards for ABL to determine the MRD response in copy number. We provide technical aspects of this approach as well as our experience with 19 patients with atypical NPM1, RUNX1 and IDH1/2 mutations. In all cases, we demonstrate a correlation between response and copy number. We further demonstrate how copy number monitoring can modulate the clinical management. Taken together, we provide proof of concept of a novel yet simple tool, which allows in-house MRD monitoring for identified mutations, with ABL-based commercial standards. This approach would facilitate large multi-center studies assessing the clinical relevance of selected MRD monitoring.
KW - acute myeloid leukemia
KW - measurable residual disease
KW - plasmid base
UR - http://www.scopus.com/inward/record.url?scp=85178142594&partnerID=8YFLogxK
U2 - 10.3390/cancers15225360
DO - 10.3390/cancers15225360
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C2 - 38001621
AN - SCOPUS:85178142594
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 22
M1 - 5360
ER -