Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal arterial walls in healthy individuals in China

Abstract In chronic myeloid leukemia (CML) the p210 BCR-ABL protein, generated by a t(9;22)(q34;q11) translocation, is the underlying mechanism of leukemogenesis. Although the presence of p210 BCR-ABL is normally restricted to CML patients (pts), previous reports demonstrated low levels of bcr-abl transcripts in healthy individuals that may be controlled by an intact immune system (Bose et al. Blood92:3362, 1998). Interestingly, several articles reported cases of CML occurring in pts after SOT (Pelloso et al. Leukemia Res29:353, 2005). Therefore, immunosuppressed SOT recipients should represent an optimal population to investigate the frequency of bcr-abl transcripts in non-leukemic individuals in order to address a potential impact of immunosuppression on the presence of bcr-abl transcripts. This possibility was investigated by studying peripheral blood leukocytes for the presence of bcr-abl transcripts in a total of 201 individuals of whom 100 were SOT recipients (n=50 kidney, n=46 liver, n=3 heart, n=1 heart-lung) and 101 were control individuals (n=87 patients with renal failure, n=14 healthy individuals). The male to female ratio in the study group was 54:46 (median age: 55.38 years, range: 22–83) and matched the control group (median age: 59.8 years, range: 32–96). Included in the study group were 13 pts with post transplant malignancies who were previously treated with standard chemotherapeutic regimens. Immune suppressive drugs given to all SOT recipients included steroids (90%), cyclosporine A (69%), azathioprine (22%), tacrolimus (69%), sirolimus (44%), mycophenolic acid (63%) and others (37%). For the detection of the bcr-abl transcript we used a nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay that is routinely used in our institution. All samples were tested at least twice. In 5/100 immunosuppressed pts at least 1 of 2 RT-PCR products was bcr-abl positive in the second round amplification. This rate significantly exceeded the control group that was completely bcr-abl negative (0/101 p = 0.0242). Of the 5 bcr-abl positive pts, 3 were liver transplant and 2 were kidney transplant recipients. The latency in this group (interval between transplantation and bcr-abl PCR) was at 58.4 months (range: 24-135 months) and shorter when compared to the latency in the remaining study group (104.8 months; range 1 – 369). Additionally, all samples were tested for both the pml-rara and aml1-eto transcripts that are detectable in subsets of pts with acute myeloid leukaemia but none of the samples tested positive for these transcripts. Our findings are extended by three case reports of SOT recipients (2 kidney, 1 liver) who developed CML in a total of 2088 transplantations in our centre in 9 years. In these three pts (2 males, 1 female), CML occurred at 84.3 months (range: 32–183) following SOT. In summary our data show: 1. The presence of bcr-abl transcripts in immunosuppressed non-leukemic SOT pts and the absence of bcr-abl transcripts in healthy normals when tested with routine PCR protocols. 2. The absence of pml-rara and aml1-eto transcripts in both the study and control group. And 3. the occurrence of CML in three patients following SOT suggesting a higher frequency of CML in this population.

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Differential expression and regulation of the non-integrin 37/67-kDa laminin receptor on peripheral blood leukocytes of healthy individuals and patients with rheumatoid arthritis

Scientific Reports ◽

10.1038/s41598-018-37907-7 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Barry A. Kane ◽

Hongyan An ◽

Poornima Rajasekariah ◽

H. Patrick McNeil ◽

Katherine Bryant ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Differential Expression ◽

Peripheral Blood ◽

Laminin Receptor ◽

Healthy Individuals ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes

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Deoxyribonucleic acid methylation in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes in blood vessels and cells in patients with carotid atherosclerosis

Russian Journal of Cardiology ◽

10.15829/1560-4071-2020-4060 ◽

2020 ◽

Vol 25 (10) ◽

pp. 4060

Author(s):

Yu. A. Koroleva ◽

A. V. Markov ◽

I. A. Goncharova ◽

A. A. Sleptsov ◽

N. P. Babushkina ◽

...

Keyword(s):

Dna Methylation ◽

Peripheral Blood ◽

Methylation Level ◽

Deoxyribonucleic Acid ◽

Healthy Individuals ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Blood Samples ◽

Cpg Sites ◽

Atherosclerotic Lesions

Aim. Comparative analysis of the deoxyribonucleic acid (DNA) methylation level in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes (9p21.3 locus) in vessels with/without atherosclerotic lesions, as well as in leukocytes of patients with clinically relevant carotid artery (CA) atherosclerosis and healthy individuals.Material and methods. The group of patients with clinically relevant atherosclerosis included 22 individuals with severe stenosis (>80%) of CA. Samples of atherosclerotic plaques, presenting CA regions, and great saphenous veins, as well as peripheral blood samples (leukocytes) were obtained from patients. The control group consisted of 14 individuals with the mild CA stenosis (£24%) and without hemodynamically relevant changes; peripheral blood samples were obtained from each of them. DNA methylation level was assessed by targeted bisulfite sequencing of amplicons.Results. The tissue-specific methylation of 31 CpG-site in the CDKN2A/2B and CDKN2B-AS1 gene enhancer was established: the vascular tissues significantly differed from the peripheral blood leukocytes. At the same time, there was an increase in the methylation level of both certain CpG sites and whole analyzed CA region affected by atherosclerosis (48,6 [34,8; 62,0]%), compared with intact vessels, both arteries (25,2 [23,1; 41,60]%, p=0,0001) and veins (35,0 [31,6; 40,0]%, p=0,0039). Patients had lower methylation levels in all CpG sites in blood leukocytes compared to blood vessel samples (8,7 [6,1; 9,7]%; p<0,05). At the same time, the level of DNA methylation in the blood leukocytes of atherosclerotic patients does not differ from that in healthy individuals (9,3 [8,3; 13,6]%; p>0,8).Conclusion. In the present study, the relationship between an increase in the DNA methylation in the enhancer of the CDKN2A/2B and CDKN2B-AS1 genes in CA and their atherosclerotic lesions was revealed, as well as the tissue-specific DNA methylation between vessels and peripheral blood leukocytes.

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