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2nd Edition: Minimal Residual Disease of Cancers

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 6446

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Special Issue Editor

Dr. Andrei Tchirkov

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Guest Editor

Imagerie Moléculaire et Stratégies Théranostiques Faculté de Médecine, Unité INSERM 1240, Université Clermont Auvergne, CHU Clermont-Ferrand, 63003 Clermont Ferrand, France
Interests: minimal residual disease (MRD); hematological malignancies; pediatric tumors; digital PCR; new generation sequencing (NGS); telomere biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the Special Issue “Minimal Residual Disease of Cancers” (https://www.mdpi.com/journal/cancers/special_issues/mrdc).

Minimal residual disease (MRD) is a very small population of cancer cells that persists in a patient in morphologic complete remission (CR) after treatment. The development in the late 1980s of highly sensitive molecular tools based on the polymerase chain reaction (PCR) amplification of DNA sequences and mRNA transcripts resulting from tumor-specific chromosomal translocations has created opportunities to study MRD. After the introduction of quantitative real-time PCR, this approach has become a gold-standard method for MRD testing. Alternative approaches have been developed using the detection of tumor cell antigens with sensitive immunological methods. Finally, gene mutations are being increasingly used as biomarkers for MRD detection in liquid biopsies using digital droplet PCR and new generation sequencing.

As a result of these technological advances, there is a growing number of clinical applications of MRD measurement in a variety of hematological and solid tumors. Moreover, the introduction of effective targeted therapies and drug combinations has increased the rate of patients in CR who need MRD monitoring. Accurate measurement of MRD enables specialists to better assess treatment response, patient prognosis, and the risk of relapse. In several cancers, MRD assessment is now a part of routine investigations and a novel endpoint in clinical trials. However, many challenges remain. They concern the clinical significance of MRD in some cancers, the functional assessment of residual tumor cells, and the development of specific MRD-targeting approaches. This Special Issue will give us an excellent opportunity to highlight the most recent MRD applications and concepts, which can ultimately help to guide specialists’ treatment decisions in patients with cancer.

Dr. Andrei Tchirkov
Guest Editor

Manuscript Submission Information

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Keywords

minimal residual disease (MRD)
hematological malignancies
solid tumors
MRD biomarkers
real-time PCR
digital PCR
NGS
immunological MRD detection
functional MRD assays
MRD targeting

Published Papers (3 papers)

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Research

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17 pages, 2341 KiB

Open AccessArticle

Measurable Residual Disease Monitoring by Locked Nucleic Acid Quantitative Real-Time PCR Assay for IDH1/2 Mutation in Adult AML

by Hsiao-Wen Kao, Ming-Chung Kuo, Ying-Jung Huang, Hung Chang, Shu-Fen Hu, Chein-Fuang Huang, Yu-Shin Hung, Tung-Liang Lin, Che-Wei Ou, Ming-Yu Lien, Jin-Hou Wu, Chih-Cheng Chen and Lee-Yung Shih

Cancers 2022, 14(24), 6205; https://doi.org/10.3390/cancers14246205 - 15 Dec 2022

Cited by 3 | Viewed by 1503

Abstract

Locked nucleic acid quantitative Real-Time PCR (LNA-qPCR) for IDH1/2 mutations in AML measurable residual disease (MRD) detection is rarely reported. LNA-qPCR was applied to quantify IDH1/2 mutants MRD kinetics in bone marrow from 88 IDH1/2-mutated AML patients, and correlated with NPM1-MRD, clinical characteristics, and outcomes. The median normalized copy number (NCN) of IDH1/2 mutants decreased significantly from 53,228 (range 87–980,686)/ALB × 10⁶ at diagnosis to 773 (range 1.5–103,600)/ALB × 10⁶ at first complete remission (CR). IDH1/2 LNA-qPCR MRD was concordant with remission status or NPM1-MRD in 79.5% (70/88) of patients. Younger patients and patients with FLT3 mutations had higher concordance. The Spearman correlation coefficient (r_s) and concordance rate between the log reduction of IDH1/2 LNA-qPCR and NPM1-MRD were 0.68 and 81% (K = 0.63, 95% CI 0.50–0.74), respectively. IDH1/2-MRD > 2 log reduction at first CR predicted significantly better relapse-free survival (3-year RFS rates 52.9% vs. 31.9%, p = 0.007) and cumulative incidence of relapse (3-year CIR rates 44.5% vs. 64.5%, p = 0.012) compared to IDH1/2-MRD ≤ 2 log reduction. IDH1/2-MRD > 2 log reduction during consolidation is also associated with a significantly lower CIR rate than IDH1/2-MRD ≤ 2 log reduction (3-year CIR rates 42.3% vs. 68.8%, p = 0.019). LNA-qPCR for IDH1/2 mutation is a potential MRD technique to predict relapse in IDH1/2-mutated AML patients, especially for those with IDH1/2 MRD > 2 log reduction at first CR or a concurrent FLT3 mutation. Full article

(This article belongs to the Special Issue 2nd Edition: Minimal Residual Disease of Cancers)

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14 pages, 820 KiB

Open AccessArticle

Reliable Flow-Cytometric Approach for Minimal Residual Disease Monitoring in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia after CD19-Targeted Therapy

by Ekaterina Mikhailova, Olga Illarionova, Alexander Komkov, Elena Zerkalenkova, Ilgar Mamedov, Larisa Shelikhova, Yulia Olshanskaya, Natalia Miakova, Galina Novichkova, Alexander Karachunskiy, Michael Maschan and Alexander Popov

Cancers 2022, 14(21), 5445; https://doi.org/10.3390/cancers14215445 - 05 Nov 2022

Cited by 9 | Viewed by 2241

Abstract

We aimed to develop an antibody panel and data analysis algorithm for multicolor flow cytometry (MFC), which is a reliable method for minimal residual disease (MRD) detection in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated with CD19-directed therapy. The development of the approach, which was adapted for the case of possible CD19 loss, was based on the additional B-lineage marker expression data obtained from a study of primary BCP-ALL patients, an analysis of the immunophenotypic changes that occur during blinatumomab or CAR-T therapy, and an analysis of very early CD19-negative normal BCPs. We have developed a single-tube 11-color panel for MFC-MRD detection. CD22- and iCD79a-based primary B-lineage gating (preferably consecutive) was recommended. Based on patterns of antigen expression changes and the relative expansion of normal CD19-negative BCPs, guidelines for MFC data analysis and interpretation were established. The suggested approach was tested in comparison with the molecular techniques: IG/TR gene rearrangement detection by next-generation sequencing (NGS) and RQ-PCR for fusion-gene transcripts (FGTs). Qualitative concordance rates of 82.8% and 89.8% were obtained for NGS-MRD and FGT-MRD results, respectively. We have developed a sensitive and reliable approach that allows MFC-MRD monitoring after CD19-directed treatment, even in the case of possible CD19 loss. Full article

(This article belongs to the Special Issue 2nd Edition: Minimal Residual Disease of Cancers)

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Review

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25 pages, 732 KiB

Open AccessReview

Minimal Residual Disease in Multiple Myeloma: Past, Present, and Future

by Alejandro Medina-Herrera, María Eugenia Sarasquete, Cristina Jiménez, Noemí Puig and Ramón García-Sanz

Cancers 2023, 15(14), 3687; https://doi.org/10.3390/cancers15143687 - 20 Jul 2023

Cited by 2 | Viewed by 2083

Abstract

Responses to treatment have improved over the last decades for patients with multiple myeloma. This is a consequence of the introduction of new drugs that have been successfully combined in different clinical contexts: newly diagnosed, transplant-eligible or ineligible patients, as well as in the relapsed/refractory setting. However, a great proportion of patients continue to relapse, even those achieving complete response, which underlines the need for updated response criteria. In 2014, the international myeloma working group established new levels of response, prompting the evaluation of minimal residual disease (MRD) for those patients already in complete or stringent complete response as defined by conventional serological assessments: the absence of tumor plasma cells in 100,000 total cells or more define molecular and immunophenotypic responses by next-generation sequencing and flow cytometry, respectively. In this review, we describe all the potential methods that may be used for MRD detection based on the evidence found in the literature, paying special attention to their advantages and pitfalls from a critical perspective. Full article

(This article belongs to the Special Issue 2nd Edition: Minimal Residual Disease of Cancers)

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