Table 1.

Characteristics of the currently used MRD methods

MRD methodTechniqueMarkersPatient materialLeukemia typeSensitivityAdvantageDisadvantageRelevant references
Molecular 
 rearrangements RT-qPCR IGH DNA ALL 10−4 to 10−5 Patient specific Requires diagnosis sample. Clonal evolution missed. 4,5,64,65  
ddPCR TCR Myeloma Standardized method 
  CLL  
 NGS  DNA ALL 10−3 to 10−6 Does not require construction of patient-specific reagents; may detect clone shifts. Expensive 66  
Including clonoSEQ assay Myeloma 
 CLL 
  Fusion genes RT-qPCR BCR/ABL RNA ALL, CML 10−4 to 10−5 Standardized primers Applicable in a limited number of patients 32,33,56,67  
AML/ETO AML 
CBFB-MYH11 AML 
PML/RARa APL 
RUNX1/RUNX1T1 ALL, AML 
BCL3 translocations CLL 
Less common fusions  
  Mutations RT-qPCR NPM1 RNA AML 10−4 to 10−7 Extremely sensitive Applicable in a limited number of patients (∼30%). Clonal evolution missed. 31,68  
 NGS Mutation panels DNA AML 10−3 to 10−5 Applicable in many patients Requires further development for assay harmonization/standardization. Insensitive without error correction. 37  
May detect clone shift 
 Overexpression RT-qPCR WT1 RNA AML 10−5 Sensitive Applicable in a limited number of patients 36,51,69,70  
Immunophenotypic 
 Leukemia/myeloma associated immune phenotype Distinctive antibody panels Diagnosis and follow-up cells AML 10−4 More informative with diagnosis sample Clonal evolution missed. Immunophenotypic profiles required. 71-73  
ALL Almost all patients 
CLL Relatively fast 
Myeloma  
  Different from normal Distinctive antibody panels Follow-up cells only AML 10−4 Almost all patients. Relatively fast. Extensive knowledge of normal and regenerating bone marrow required 74  
  Leukemia stem cells CD34+/CD38 including distinctive antibody panels Diagnosis and follow-up cells AML 10−6 High prognostic relevance to identify a poor risk group Only CD34+ leukemia. Large number of cells required. 61  
MRD methodTechniqueMarkersPatient materialLeukemia typeSensitivityAdvantageDisadvantageRelevant references
Molecular 
 rearrangements RT-qPCR IGH DNA ALL 10−4 to 10−5 Patient specific Requires diagnosis sample. Clonal evolution missed. 4,5,64,65  
ddPCR TCR Myeloma Standardized method 
  CLL  
 NGS  DNA ALL 10−3 to 10−6 Does not require construction of patient-specific reagents; may detect clone shifts. Expensive 66  
Including clonoSEQ assay Myeloma 
 CLL 
  Fusion genes RT-qPCR BCR/ABL RNA ALL, CML 10−4 to 10−5 Standardized primers Applicable in a limited number of patients 32,33,56,67  
AML/ETO AML 
CBFB-MYH11 AML 
PML/RARa APL 
RUNX1/RUNX1T1 ALL, AML 
BCL3 translocations CLL 
Less common fusions  
  Mutations RT-qPCR NPM1 RNA AML 10−4 to 10−7 Extremely sensitive Applicable in a limited number of patients (∼30%). Clonal evolution missed. 31,68  
 NGS Mutation panels DNA AML 10−3 to 10−5 Applicable in many patients Requires further development for assay harmonization/standardization. Insensitive without error correction. 37  
May detect clone shift 
 Overexpression RT-qPCR WT1 RNA AML 10−5 Sensitive Applicable in a limited number of patients 36,51,69,70  
Immunophenotypic 
 Leukemia/myeloma associated immune phenotype Distinctive antibody panels Diagnosis and follow-up cells AML 10−4 More informative with diagnosis sample Clonal evolution missed. Immunophenotypic profiles required. 71-73  
ALL Almost all patients 
CLL Relatively fast 
Myeloma  
  Different from normal Distinctive antibody panels Follow-up cells only AML 10−4 Almost all patients. Relatively fast. Extensive knowledge of normal and regenerating bone marrow required 74  
  Leukemia stem cells CD34+/CD38 including distinctive antibody panels Diagnosis and follow-up cells AML 10−6 High prognostic relevance to identify a poor risk group Only CD34+ leukemia. Large number of cells required. 61  

CML, chronic myeloid leukemia; ddPCR, droplet digital PCR; NGS, next-generation sequencing; RT-qPCR, reverse-transcription quantitative polymerase chain reaction.

View Large
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal