Abstract
Minimal residual disease (MRD) refers to a chemotherapy/radiotherapy-surviving leukemia cell population that gives rise to relapse of the disease. The detection of MRD is critical for predicting the outcome and for selecting the intensity of further treatment strategies. The development of various new diagnostic platforms, including next-generation sequencing (NGS), has introduced significant advances in the sensitivity of MRD diagnostics. Here, we review current methods to diagnose MRD through phenotypic marker patterns or differential gene patterns through analysis by flow cytometry (FCM), polymerase chain reaction (PCR), real-time quantitative polymerase chain reaction (RQ-PCR), reverse transcription polymerase chain reaction (RT-PCR) or NGS. Future advances in clinical procedures will be molded by practical feasibility and patient needs regarding greater diagnostic sensitivity.
Highlights
Minimal residual disease (MRD) levels are used to modify the intensity and duration of chemotherapy and to create risk profiles for patients based on measured clearance of leukemic cells and post-treatment probability of disease relapse correlated to MRD levels
The clinical significance of the 0.01% MRD cutoff level is that when a patient has cellular MRD levels ≥0.01% in a bone marrow sample at important measurement time points during therapy, the patient will have a significantly higher risk for leukemia relapse than if MRD levels are less than 0.01% [3,4,5]
MRD cells display differential presentation of cellular markers over time compared to normal B cells; treatment samples of MRD measured by flow cytometry (FCM) taken during induction phase relapse therapy can be reliable because, in most cases, MRD cell populations generally resemble diagnostic leukemic phenotypes
Summary
Minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is the presence of post-therapeutic (chemotherapy, immunotherapy, or radiotherapy) leukemia cells within the bone marrow and more rarely in peripheral blood circulation. MRD levels are used to modify the intensity and duration of chemotherapy (which may include allogeneic stem cell transplantation) and to create risk profiles for patients based on measured clearance of leukemic cells and post-treatment probability of disease relapse correlated to MRD levels. The most important mutation outcomes from LSCs are the capacity for unlimited self-renewal and developmental arrest at the pre-lymphocyte developmental stage These cell profiles can be the result of several factors, including the aberrant expression of proto-oncogenes, chromosomal translocations that express fusion genes that encode transcription factors and active kinases, and post-mitotic aneuploid cell development [17]. Chemotherapy sequelae can include secondary leukemias, tumors, cardiomyopathy, and neuropsychological problems, among other symptoms
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