Role of Circulating Tumor DNA in Hematological Malignancy

Ogawa, Miho; Yokoyama, Kazuaki; Imoto, Seiya; Tojo, Arinobu

doi:10.3390/cancers13092078

Cited by 12 publications

(7 citation statements)

References 165 publications

(153 reference statements)

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“…Detection of MRD in PB mirroring BM and/or EMD would bring obvious advantages to patients and clinicians, allowing frequent and minimally invasive real-time monitoring of the disease [ 83 , 84 , 85 , 86 ]. In fact, the use of a liquid biopsy has been proposed as an alternative approach to monitoring MRD in MM and mainly uses circulating tumor DNA (ctDNA) [ 83 , 87 , 88 ], circulating tumor cells (CTCs) [ 89 , 90 , 91 ], serum monoclonal immunoglobulins [ 14 ], and, recently, EVs [ 44 , 92 ].…”

Section: Resultsmentioning

confidence: 99%

Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept

Bergantim

Silva

Polónia

et al. 2022

IJMS

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Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD.

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Section: Resultsmentioning

confidence: 99%

Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept

Bergantim

Silva

Polónia

et al. 2022

IJMS

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“…Diverse biomarkers can be used to track response and risk of relapse. PET imaging and ctDNA analyses have emerged as sensitive means of tracking lymphoma and leukemia regression (48)(49)(50). Q-PCR or deep sequencing methods have provided a picture of CAR-19 expansion and persistence over the first critical weeks and months after treatment (51).…”

Section: Discussionmentioning

confidence: 99%

CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma

Su¹,

Wu²,

Lobb³

et al. 2022

Preprint

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B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within six months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents CD19 antigen-loss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.

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“…Several molecular testing and biomarkers have been evaluated for detection and diagnosis of hematologic cancers. These include: somatic mutations in preleukaemic hematopoietic stem and progenitor cells (HSPCs), presence of tumor-specific mutations in cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) [ 7 , 13 , 14 , 15 ]. In our study, an increase in the peripheral blood levels of CD24/CD11b was found among subjects with hematologic malignancies compared to healthy subjects ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies

Shapira

Kazanov²,

Mdah

et al. 2021

JPM

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An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7–86.3%) and specificity of 80.2% (95% CI, 76.1–84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.

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Role of Circulating Tumor DNA in Hematological Malignancy

Cited by 12 publications

References 165 publications

Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept

Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept

CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies

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