# NGS-based MRD (clonoSEQ and molecular MRD)

Source: https://onco.cc/technologies/ngs-mrd-clonoseq/  
OnCo record `ngs-mrd-clonoseq` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million.

## Summary

clonoSEQ (Adaptive Biotechnologies) tracks clonal IGH/TCR rearrangements at 10^-6 and is FDA-cleared for ALL, myeloma, and CLL. In AML, quantitative PCR of NPM1 or core-binding-factor fusion transcripts and error-corrected NGS of persistent mutations (excluding DNMT3A/TET2/ASXL1) define molecular MRD per ELN 2021. MRD status now drives transplant decisions in AML, blinatumomab use in ALL, and fixed-duration versus continuous therapy debates in CLL.

## Fields

- Kind: Technology
- Status: standard-of-care
- Last checked: 2026-09-07
- Principle: The assay deep-sequences a patient-specific clonotype or mutation with error correction.
- Strengths: 10^-5 to 10^-6 sensitivity; Blood-based monitoring in many settings
- Limitations: Requires a baseline sample to identify the clone; Persisting pre-leukaemic clones (CHIP) confound AML MRD

## Notes

- Lymphoma: the patient-specific immunoglobulin or T-cell receptor sequence found at diagnosis becomes the residual disease marker afterwards, which is why clonality testing and residual disease testing are the same assay read twice. The BIOMED-2 primer design is the ancestor of the sequencing versions (van Dongen 2003).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Minimal_residual_disease
- Wikipedia: https://en.wikipedia.org/wiki/Minimal_residual_disease
- van Dongen et al., Leukemia 2003: BIOMED-2 multiplex PCR for clonal immunoglobulin and T-cell receptor rearrangements: https://doi.org/10.1038/sj.leu.2403202

## Connected records

- technologies: [Immunoglobulin and T-cell receptor clonality testing](https://onco.cc/technologies/clonality-testing/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Residual disease kinetics (BCR-ABL halving and ctDNA slopes)](https://onco.cc/technologies/mrd-kinetics-models/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Adolescent and young adult cancers (ages 15 to 39)](https://onco.cc/cancers/aya-cancers/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [FLT3-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-flt3/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Newly diagnosed multiple myeloma, transplant-eligible](https://onco.cc/cancers/myeloma-transplant-eligible/), [Newly diagnosed multiple myeloma, transplant-ineligible](https://onco.cc/cancers/myeloma-transplant-ineligible/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/), [Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)](https://onco.cc/cancers/all-ph-like/), [Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)](https://onco.cc/cancers/all-paediatric-ph-positive/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/), [Standard-risk B-cell acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-standard-risk/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- companies: [Adaptive Biotechnologies](https://onco.cc/companies/adaptive-biotechnologies/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/)
- trials: [myeloMATCH](https://onco.cc/trials/myelomatch/)
- ideas: [MRD-guided transplant decisions in intermediate-risk AML](https://onco.cc/ideas/idea-mrd-guided-transplant-aml/), [MRD-guided treatment duration in CLL](https://onco.cc/ideas/idea-mrd-guided-stop-cll/), [Reference materials and open proficiency testing for residual disease tests](https://onco.cc/ideas/idea-bio2-mrd-reference-standards/), [Transplant-free Ph-positive ALL for MRD-negative adults](https://onco.cc/ideas/idea-transplant-free-ph-all/), [Watch the immune system's response in the blood three weeks in](https://onco.cc/ideas/idea-bio2-tcr-repertoire-early-readout/)
- biomarkers: [Immunoglobulin and T-cell receptor clonality](https://onco.cc/biomarkers/ig-tcr-clonality/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- drugs: [clonoSEQ](https://onco.cc/drugs/clonoseq/)

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