Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Mutation Detection
2.3. Measurable Residual Disease Monitoring
2.4. Linearity and Limit of Detection
3. Results
3.1. Generation and Validation of Plasmid-Base PCR for MRD Monitoring
3.2. Patient Characteristics and Mutation Profile
3.2.1. RUNX1 Monitoring
3.2.2. NPM1 Monitoring
3.2.3. IDH1/2 Monitoring
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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# | Sex | ECOG | Age | BM Blasts % | WBC Dx | Karyo-Type | Co-Mutations | DN/Sec | Plasmid Mutation | Induction | Salvage/ Consolidation | BMT | Death Cause | FU |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | M | 1 | 61 | 1.7 | 1.5 | −7Q | TET2 DNMT3 FLT3 | Sec-TR | Runx1 | azacitidine | pevonidestat | no | MM | 30 m |
2 | M | 2 | 72 | 22 | 4.30 | Nk | TET2 SRSF2 SF3B1 | DN | Runx1 | Aza + ven | gilteritinib | MUD | 12 m | |
3 | M | 1 | 66 | 8 | 1.50 | Nk | BCORL1 SRSF2 | Sec-MDS | Runx1 | Aza + ven | MRF | 3 m | ||
4 | F | 0 | 59 | 40 | 3.5 | t3:3 | ASXL1 SF3B1 | DN | Runx1 | 7 + 3 | HAM | MUD | 36 m | |
5 | F | 1 | 91 | 22 | 65 | Nk | ASXL1 SRSF2 FLT3 | DN | Runx1 | Aza + ven | no | 13 m | ||
6 | M | 1 | 74 | 70 | 2.5 | Tetra- ploid | FLT3 IDH1 PHF6 SRSF2 | DN | Runx1 | Aza + ven | no | 10 m | ||
7 | F | 0 | 39 | 20 | 7.1 | Nk | BCOR WT1 DNMT3A KIT | DN | Runx1 | 7 + 3 + mido | flag + ida + ven | MRM | 9 m | |
8 | M | 2 | 76 | 50 | 0.9 | iso14 | BCOR SRSF2 TET2 | DN | Runx1 | Decitabine (trial)r | Aza + ven | no | 82 m | |
9 | F | 0 | 55 | 65 | 77 | Nk | CEBPA TET2 MYC | DN | NPM1 | 7 + 3 | HIDAC | HAP | acute GVHD | 19 m |
10 | F | 0 | 48 | 30 | 9.9 | t3:11 | FLT3 | DN | NPM1 | 7 + 3 + mido | HIDAC | MUD | 16 m | |
11 | F | 2 | 42 | 30 | 1.90 | Nk | PTPN11 TET2 | Sec-TR | NPM1 | Aza + ven | MUD | 24 m | ||
12 | F | 0 | 19 | 80 | 1.30 | Nk | None | DN | NPM1 | 7 + 3 | HIDAC | MUD | 58 m | |
13 | M | 0 | 24 | 60 | 1.5 | Nk | None | DN | NPM1 | 7 + 3 + mido | HIDAC | no | 35 m | |
14 | M | 2 | 81 | 45 | 1.9 | Nk | ASXL1 STAT3 STAG2 SRSF2 | Sec-MDS | IDH2 | Aza + ven | no | Re-AML | 15 m | |
15 | M | 0 | 60 | 45 | 9 | tri11 | U2AF1 DMNT3A | DN | IDH2 | 7 + 3 | flag + ida + ven | MUD | 10 m | |
16 | F | 2 | 62 | 70 | 3.7 | mon7 | BCOR DNMT3A EZH2 | DN | IDH2 | Aza + ven | MRM | 17 m | ||
17 | M | 2 | 69 | 50 | 1.4 | Nk | RUNX1 | DN | IDH2 | Aza + ven | no | 22 m | ||
18 | F | 1 | 57 | 10 | 1.6 | Nk | JAK2 MPL DMNT3A | Sec-ET | IDH2 | Aza + ven | MUD | 15 m | ||
19 | M | 1 | 77 | 85 | 2.4 | tri8 | SRSF2 BCOR RUNX1 | DN | IDH1 | Aza + ven +/− magro (trial) | no | 4 m |
RUNX1 Patient | Diagnosis | Post Induction | Post Salvage | Post Consolidation | Post-Transplant 1 m | FU 3 M | FU 6 M | FU 12 M | |||
---|---|---|---|---|---|---|---|---|---|---|---|
2 | IP | 40% | 10% | 4% | 3.1% | 1% | 1.5% | ||||
STR | BM 100% | BM 100% | |||||||||
RUNX1 qPCR CN/105ABL | 61,023 | 61,369 | 66,152 | 56,979 | 315 | ||||||
4 | IP | 40% | 40% | 2.6% | 2.2% | 2.6% | 1.6% | 1.4% | 1.5% | ||
STR | BM 100% | BM 100% | BM 97% | BM 100% | |||||||
RUNX1 qPCR CN/105ABL | 436,945 | neg | neg | neg | neg | ||||||
7 | IP | 20% | 15% | 1.4% | 1.4% | 1.4% | |||||
STR | BM 100% | BM 100% | |||||||||
RUNX1 qPCR CN/105ABL | 16,459 | 14,505 | 260 | neg | neg | ||||||
NPM1 Patient | Diagnosis | Post Induction | Post Consol. | Post Consol. | FU 3 M | FU 4 M | Post MRD Eraser cy 1 | Post MRD Eraser cy 2 | Post-Transplant 1 m | FU 3M | |
9 | IP | 65% | 1.7% | 1.8% | 2.4% | 1.5% | 2% | 2% | 0.8% | 2.7% | |
STR | BM 58% | ||||||||||
NPM1 qPCR CN/105ABL | 168,717 | 73,274 | 68 | 45 | 258 | 36,362 | 39 | neg | |||
10 | IP | 30% | 3% | 0.6% | 1.8% | 1.2% | 1% | ||||
STR | BM 100% | BM 100% | |||||||||
NPM1 qPCR CN/105ABL | 1,038,889 | 15,557 | 239 | 79 | neg | neg | |||||
IDH Patient | Diagnosis | Post Induction | Post Consol./Salvage | Post-Transplant 3 m | FU 6 M | FU 9 M | FU 12 M | ||||
15 | IP | 45% | 10% | 1.5% | 2% | ||||||
STR | BM 100% | ||||||||||
IDH2 qPCR CN/105ABL | 96,964 | 967 | neg | ||||||||
16 | IP | 35% | 3.3% | 5% | 1.8% | 1.4% | |||||
STR | BM 100% | BM100% | |||||||||
IDH2 qPCR CN/105ABL | 45,308 | neg | 106 | neg | neg | ||||||
18 | IP | 10% | 2.5% | 2.2% | 0.8% | 1.8% | 1.2% | ||||
STR | BM 98% | BM 100% | BM 100% | ||||||||
IDH2 qPCR CN/105ABL | 8911 | 50,659 | neg | neg | 70 | neg |
Patient | Diagnosis | Post Induction/ 1st Aza + Ven Cyc | Post Consol. | Post Consol. | FU 3 M/ Post 3 Aza + Ven Cycles | FU 6 M/ Post 6 Aza + Ven Cycles | FU 8 M/ Post 8 Aza + Ven Cycles | FU 12 M/ Post 12 Aza + Ven Cycles | FU 24 M/ Post 24 Aza + Ven Cycles | |
---|---|---|---|---|---|---|---|---|---|---|
13 | IP | 60% | 4% | 1.9% | 2.3% | 2.1% | 2% | 1.3% | 1.5% | |
NPM1 qPCR CN/105ABL | 1,414,578 | 216 | 45 | 40 | 3.2 | 0.76 | ||||
17 | IP | 50% | 2.5% | 2.6% | 1.1% | 1.5% | 0.5% | |||
IDH2 qPCR CN/105ABL | 115,521 | 57,677 | 4681 | 2149 | 2243 | 403 |
Patient | Diagnosis | Post Induction | Post Consol. | FU 12 M | FU 24 M | FU 30 M | FU 33 M | FU 36 M | FU 37 M | Post Salvage | FU 6 M | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
12 | IP | 63% | 3.5% | 1.6% | 2.5% | 2.6% | 3% | 10% | 18% | 26% | 1% | 2% |
STR | BM 100% | |||||||||||
NPM1 qPCR CN/105ABL | 3,221,400 | 49 | neg | neg | 314 | 98,700 | 463,417 | 529,710 | 828,789 | neg | neg |
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Nachmias, B.; Krichevsky, S.; Gatt, M.E.; Gross Even-Zohar, N.; Shaulov, A.; Haran, A.; Aumann, S.; Vainstein, V. Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest. Cancers 2023, 15, 5360. https://doi.org/10.3390/cancers15225360
Nachmias B, Krichevsky S, Gatt ME, Gross Even-Zohar N, Shaulov A, Haran A, Aumann S, Vainstein V. Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest. Cancers. 2023; 15(22):5360. https://doi.org/10.3390/cancers15225360
Chicago/Turabian StyleNachmias, Boaz, Svetlana Krichevsky, Moshe E. Gatt, Noa Gross Even-Zohar, Adir Shaulov, Arnon Haran, Shlomzion Aumann, and Vladimir Vainstein. 2023. "Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest" Cancers 15, no. 22: 5360. https://doi.org/10.3390/cancers15225360
APA StyleNachmias, B., Krichevsky, S., Gatt, M. E., Gross Even-Zohar, N., Shaulov, A., Haran, A., Aumann, S., & Vainstein, V. (2023). Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest. Cancers, 15(22), 5360. https://doi.org/10.3390/cancers15225360