Circulating cell-free DNA in hematological malignancies

Buedts, Lieselot; Vandenberghe, Peter

doi:10.3324/haematol.2015.131128

Cited by 20 publications

(25 citation statements)

References 29 publications

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“…Aside from several physiological states such as pregnancy and physical activity, pathological conditions, including inflammation and autoimmune diseases, may present with elevated cfDNA levels. In cancer, cfDNA levels may be increased up to 1000 ng/mL, which draws attention to an association between cfDNA levels and tumor burden (1,4,8,(10)(11)(12)(13). A previously reported association between age and cfDNA was confirmed in our study.…”

Section: Discussionsupporting

confidence: 85%

“…As serum cfDNA levels are expected to be more variable than plasma levels, higher serum cfDNA levels are suggested to possibly represent an indirect tumor-related process, whereas plasma levels may be a better indicator of in vivo circulating DNA (4)(5)(6)9,15,16). Alongside WBC count, several factors may affect cfDNA analysis, such as individualized variations, diurnal rhythm, inflammatory responses, and physical stimuli (1). Although sample preference would be considered an eventual limitation for the present study, we did not mean to discriminate the impact of WBCs on the entire process, considering the potential role of leukocytes in the leukemia microenvironment.…”

Section: Cfdna: Cell-free Deoxyribonucleic Acidmentioning

confidence: 99%

“…Hematological malignancies may be considered as "liquid" tumors, because the primary involved sites are bone marrow and lymphoid tissues, along with neoplastic cells circulating in the peripheral blood (1). The amount of cell-free deoxyribonucleic acid (cfDNA) increased in patients with hematological malignancies besides a variety of solid tumors.…”

mentioning

confidence: 99%

“…In healthy individuals, cfDNA is a product of physiological hematopoietic cell cycle, including myeloid and lymphoid apoptotic cells, whereas in cancer patients, only a small amount of total cfDNA originates from neoplastic cells. The wide range of this circulating tumor DNA fraction, which differs between 0.01% and 60% of total cfDNA, depends on several tumoral features, including volume, stage, vascularization, proliferation, and apoptosis rate (1,2,4,(7)(8)(9). To date, the predictor role of cfDNA was demonstrated in a wide spectrum of malignancies, including hematological disorders such as AML, MDS, and lymphoid neoplasms (2).…”

mentioning

confidence: 99%

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The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Yeğin¹,

Can²,

Gökçen³

et al. 2020

Balkan Med J

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Background: Cell-free DNA, which may be considered as "liquid" biopsy, may serve as a diagnostic and prognostic marker not only in hematological malignancies but in solid tumors as well. Aims: To investigate the prognostic role of pre-transplant cell-free DNA levels in allogeneic hematopoietic stem cell transplant recipients. Study Design: Retrospective cohort study. Methods: A total of 177 allogeneic hematopoietic stem cell transplant recipients [median age: 36 (16-66) years; male/female: 111/66] with an initial diagnosis of acute leukemia were included in the study. Cell-free DNA was extracted from pre-transplant serum samples by using the MagNA Pure Compact Nucleic Acid Isolation Kit I with the MagNA Pure Compact instrument (Roche Diagnostics, Penzberg, Germany). Results: A positive correlation was demonstrated between cell-free DNA and age (p=0.018; r=0.177). Pre-transplant cell-free DNA levels were lower in bcr-abl (+) patients (p=0.001), while an adverse correlation was indicated between cell-free DNA and bcr-abl levels (p=0.001; r=−0.531). Acute lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented significantly lower pre-transplant cell-free DNA levels. Cell-free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long-term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cell-free DNA levels (p=0.024). Overall survival was not statistically different between high-and low-cell-free DNA groups (45.2% vs 22.5; p=0.821). Conclusion: In general, low serum levels of pre-transplant çellfree DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.

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Section: Discussionsupporting

confidence: 85%

Section: Cfdna: Cell-free Deoxyribonucleic Acidmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Yeğin¹,

Can²,

Gökçen³

et al. 2020

Balkan Med J

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“…Detecting ctDNA from blood plasma and serum is challenging as it accounts only for a small fraction (less than 1%) of the total amount of cfDNA, and preanalytical processes including blood collection, purification, and storage are not yet fully standardized [19]. For ctDNA analysis, blood plasma is preferred over serum due to less contamination with genomic DNA (gDNA) by blood cell lysis, which occurs during clotting (17).…”

Section: Introductionmentioning

confidence: 99%

Optimization of Preanalytical Variables for cfDNA Processing and Detection of ctDNA in Archival Plasma Samples

Nesic

Bødker

Terp

et al. 2021

BioMed Research International

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DNA released from cells into the peripheral blood is known as cell-free DNA (cfDNA), representing a promising noninvasive source of biomarkers that could be utilized to manage Diffuse Large B-Cell Lymphoma (DLBCL), among other diseases. The procedure for purification and handling of cfDNA is not yet standardized, and various preanalytical variables may affect the yield and analysis of cfDNA, including the purification kits, blood collection tubes, and centrifugation regime. Therefore, we aimed to investigate the impact of these preanalytical variables on the yield of cfDNA by comparing three different purification kits DNeasy Blood & Tissue Kit (Qiagen), QIAamp Circulating Nucleic Acid Kit (Qiagen), and Quick-cfDNA Serum & Plasma Kit (Zymo Research). Two blood collection tubes (BCTs), EDTA-K2 and Cell-Free DNA (Streck), stored at four different time points before plasma was separated and cfDNA purified, were compared, and for EDTA tubes, two centrifugation regimes at 2000 × g and 3000 × g were tested. Additionally, we have tested the utility of long-term archival blood samples from DLBCL patients to detect circulating tumor DNA (ctDNA). We observed a higher cfDNA yield using the QIAamp Circulating Nucleic Acid Kit (Qiagen) purification kit, as well as a higher cfDNA yield when blood samples were collected in EDTA BCTs, with a centrifuge regime at 2000 × g . Moreover, ctDNA detection was feasible from archival plasma samples with a median storage time of nine years.

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Circulating cell‐free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre‐analytical biases

Soscia

Starza

Novi

et al. 2022

Hematological Oncology

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Circulating tumor DNA (ctDNA) has become the most investigated analyte in blood. It is shed from the tumor into the circulation and represents a subset of the total cell‐free DNA (cfDNA) pool released into the peripheral blood. In order to define if ctDNA could represent a useful tool to monitor hematologic malignancies, we analyzed 81 plasma samples from patients affected by different diseases. The results showed that: (i) the comparison between two different extraction methods Qiagen (Hilden, Germany) and Promega (Madison, WI) showed no significant differences in cfDNA yield, though the first recovered higher amounts of larger DNA fragments; (ii) cfDNA concentrations showed a notable inter‐patient variability and differed among diseases: acute lymphoblastic leukemia and chronic myeloid leukemia released higher amounts of cfDNA than chronic lymphocytic leukemia, and diffuse large B‐cell lymphoma released higher cfDNA quantities than localized and advanced follicular lymphoma; (iii) focusing on the tumor fraction of cfDNA, the quantity of ctDNA released was insufficient for an adequate target quantification for minimal residual disease monitoring; (iv) an amplification system proved to be free of analytical biases and efficient in increasing ctDNA amounts at diagnosis and in follow‐up samples as shown by droplet digital PCR target quantification. The protocol has been validated by quality control rounds involving external laboratories. To conclusively document the feasibility of a ctDNA‐based monitoring of patients with hematologic malignancies, more post‐treatment samples need to be evaluated. This will open new possibilities for ctDNA use in the clinical practice.

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Circulating cell-free DNA in hematological malignancies

Cited by 20 publications

References 29 publications

The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Optimization of Preanalytical Variables for cfDNA Processing and Detection of ctDNA in Archival Plasma Samples

Circulating cell‐free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre‐analytical biases

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