Infection as a cause of childhood leukemia: virus detection employing whole genome sequencing

Bartenhagen, Christoph; Fischer, Ute; Korn, Klaus; Pfister, Stefan M.; Gombert, Michael; Okpanyi, Vera; Hauer, Julia; Rinaldi, Anna Maria; Bourquin, Jean‐Pierre; Eckert, Cornelia; Hu, Jianda; Ensser, Armin; Dugas, Martin

doi:10.3324/haematol.2016.155382

Cited by 19 publications

(21 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the critical roles of BM in the support and regulation of hematopoiesis, lineage-specific differentiation, as well as homing and survival of memory cells (Visnjic et al, 2004;Bowers et al, 2015), our findings call for careful consideration of the clinical implications of viral persistence. Indeed, since many of the viruses detected can reactivate, special attention should be paid to their association with the development of lymphoproliferative and/or malignant disorders (Bartenhagen et al, 2017). Furthermore, the burden of persistent infections on the engraftment, regenerative capacity, and outcomes (Ivantes et al, 2004;Nombela-Arrieta and Isringhausen, 2017) of BM transplantation deserve in-depth evaluation.…”

Section: Discussionmentioning

confidence: 99%

The Human Bone Marrow Is Host to the DNAs of Several Viruses

Toppinen

Sajantila

Pratas

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The long-term impact of viruses residing in the human bone marrow (BM) remains unexplored. However, chronic inflammatory processes driven by single or multiple viruses could significantly alter hematopoiesis and immune function. We performed a systematic analysis of the DNAs of 38 viruses in the BM. We detected, by quantitative PCRs and next-generation sequencing, viral DNA in 88.9% of the samples, up to five viruses in one individual. Included were, among others, several herpesviruses, hepatitis B virus, Merkel cell polyomavirus and, unprecedentedly, human papillomavirus 31. Given the reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for careful examination. Furthermore, the implications of persistent infections on the engraftment, regenerative capacity, and outcomes of bone marrow transplantation deserve in-depth evaluation.

show abstract

Section: Discussionmentioning

confidence: 99%

The Human Bone Marrow Is Host to the DNAs of Several Viruses

Toppinen

Sajantila

Pratas

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Infections have been suspected and reported to be associated with the development of cancer in general, and acute leukemias in particular, save for some recent reports, generally an assumption without availability of a consistent agent [136][137][138][139]. The impact of a variety of infectious organisms including Epstein-Barr virus, herpesvirus, human immunodeficiency virus (HIV), SARS, COVD-19, Human T-lymphotropic virus (HTLV-1) and others in the development of leukemia in certain patients have been hypothesized and explored [90,136,[140][141][142][143][144][145][146][147][148][149][150]. Associations, such as that of EBV and Burkett's lymphoma in the endemic area of Eastern Africa is well known.…”

Section: Infectionsmentioning

confidence: 99%

Etiology of Acute Leukemia. A Review

Tebbi¹

2021

Preprint

View full text Add to dashboard Cite

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

show abstract

“…Viral sequences in SLE RNA-seq data were detected as previously described, with some modifications (Bartenhagen et al, 2017;Moustafa et al, 2017;Nakatsu et al, 2018). In brief, read pairs with adapter sequences, N-containing bases at the 5 ′or 3 ′ -end, and low quality data and contaminating sequences and average sequence quality (Phred score) below 30 were removed using Cutadapt (version 1.9.1) keeping the following parameters, -e 0.1 -q 20,20 e 0.1 -q 20,20 -m 10 -max-n = 0.1 m 10 -max-n = 0.1.…”

Section: Workflow For the Identification Of Viral Sequencesmentioning

confidence: 99%

“…Thereafter, randomly selected viral reads of the human associated viruses were manually and visually verified by searching (blastn) against the NCBI nucleotide collection (nr/nt) database (online) and by aligning the reads to the corresponding viral genomes. Moreover, all reads, which were unmapped after the BWA and Bowtie2 alignment, were aligned to the reference genomes of seven human associated viruses with Bowtie2 (bowtie2 -very-sensitive) instead of blastn (Bartenhagen et al, 2017). The reference genomes of seven human associated viruses were selected as follows: human herpesvirus 2 strain HG52 (NC_001798.2), human herpesvirus 4 (NC_009334.1), human herpesvirus 4 complete wild type genome (NC_007605.1), human herpesvirus 5 strain Merlin (NC_006273.2), human herpesvirus 6A (NC_001664.4), human herpesvirus 6B (NC_000898.1), human herpesvirus 7 (NC_001716.2), and human herpesvirus 8 (NC_009333.1).…”

Section: Workflow For the Identification Of Viral Sequencesmentioning

confidence: 99%

“…Ultrastructural anomalies in PBMCs of patients with SLE indicated their involvement in this disease (Bariety et al, 1971). Although 94 different viruses were identified at DNA level in the blood virome of 8,240 healthy individuals (Moustafa et al, 2017) and the virome associated with childhood leukemia was analyzed in 14 pediatric acute lymphocytic leukemia patients (Bartenhagen et al, 2017), there has been no metatranscriptomic analysis of the PBMC virome in SLE patients, till date.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dysbiosis in Peripheral Blood Mononuclear Cell Virome Associated With Systemic Lupus Erythematosus

Guo

Shi

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Objective: Pathogen infection plays a role in the development and progression of systemic lupus erythematosus (SLE). Previous studies showed that peripheral blood mononuclear cells (PBMCs) harbor many viral communities. However, little is known about the viral components and the expression profiles of SLE-associated virome. We aimed to identify viral taxonomic markers of SLE that might be used in the detection of disease or in predicting its outcome.Methods: Non-human sequence data from high-throughput transcriptome sequencing of PBMC samples from 10 SLE patients and 10 healthy individuals were used for taxonomic alignment against an integrated virome reference genome database. Based on abundance profiles of SLE-associated virome species, genera, or host, Random Forests model was used to identify the viruses associated with SLE diagnostic markers. Spearman's correlation and functional clustering was used to analyze the interaction of candidate virome dysbiosis and SLE-associated differentially expressed genes.Results: A total of 419 viruses (38 human associated viruses, 350 phage, and 31 other viruses) was detected and the diversity of the PBMC virome was significantly increased in patients with SLE compared to the healthy controls (HCs). Viral taxa discriminated the cases from the controls, with an area under the receiver operating characteristic curve of 0.883, 0.695, and 0.540 for species, genus, and host, respectively. Clinical subgroup analysis showed that candidate PBMC viral markers were associated with stable-and active-stage SLE. Functional analyses showed that virome dysbiosis was mainly relevant to cellular and metabolic processes. Conclusion:We identified virome signatures associated with SLE, which might help develop tools to identify SLE patients or predict the disease stage.

show abstract

Infection as a cause of childhood leukemia: virus detection employing whole genome sequencing

Cited by 19 publications

References 25 publications

The Human Bone Marrow Is Host to the DNAs of Several Viruses

The Human Bone Marrow Is Host to the DNAs of Several Viruses

Etiology of Acute Leukemia. A Review

Dysbiosis in Peripheral Blood Mononuclear Cell Virome Associated With Systemic Lupus Erythematosus

Contact Info

Product

Resources

About