No Evidence for t(14;18)-Positive Cells in Newborns and Young Children until the Age of 10 Followed by a Linear Increase of the Prevalence in Healthy Individuals until the Age of 50 Years.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4281-4281
Author(s):  
Frank Schüler ◽  
Lars Dölken ◽  
Sandra Dölken ◽  
Carsten Hirt ◽  
Gerhard Fusch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Peripheral Blood ◽  
Age Groups ◽  
Lymphoid Tissues ◽  
Median Frequency ◽  
Healthy Individuals ◽  
Tissue Samples ◽  
Spleen Tissue ◽  
Tonsil Tissue

Abstract The t(14;18) translocation associated with follicular lymphoma can be detected in healthy individuals when highly sensitive PCR-based techniques are applied on blood and tissue samples. We studied the prevalence and frequency of t(14;18)-positive cells in a total of 632 healthy individuals (newborns to elderly adults). A standardized quantitative real-time PCR was carried out for the detection of t(14;18)-MBR-positive cells [Dölken,L. et al.; Biotechniques1998;25:1058–1064]. The K-ras wild-type gene served as reference gene to determine the number of cells in a given sample. The individuals under study were divided into eight age groups (A: 0–9; B: 10–19; C: 20–29; D: 30–39, E: 40–49; F: 50–59; G: 60–69; H: 70–91 years). The prevalence of t(14;18) positive cells within these ten groups strongly correlates with age (χ2 Test: P < 0.0001). Until the age of 10 no individual (n=87; cord blood samples: n=36, 0–1 year: n=12; 1–9 years: n=39) had detectable circulating t(14;18)-positive cells. In the age groups between 10 to 50 years (n=336) the prevalence of circulating t(14;18)-positive cells shows a significant increase from each younger to the following older age group (Fisher’s exact test; each p value significant). The prevalence rises by a constant linear rate of 1.62% per year (r2=0.9945) beginning in a median age of 7.7 years (prevalence=1.62*[years]−7.7). We did not observe any further increase in the prevalence in individuals older than 50 years of age. The median frequencies of t(14;18) positive cells in the seven age groups from 10 – 91 years show an association with age (Kruskall Wallis test: P=0.0009). A one-by-one comparison of the seven age groups that had circulating t(14;18) positive cells (10–91 years) showed a significantly higher median frequency of t(14;18) positive cells in the two oldest age groups G (60–69yrs.) and H (70–91) than in younger groups (Mann Whitney test). Therefore, we were interested in determining the age when t(14;18) positive cells appear in different lymphoid tissues as well as peripheral blood and bone marrow. 12 tonsil samples with no pathological abnormality were obtained from 12 newborns. There were no detectable t(14;18)-positive cells in all cases. From further 11 individuals we analyzed peripheral blood, bone marrow, tonsil tissue, spleen tissue and lymph node tissue for t(14;18)-positive cells. Two individuals younger than 1 year had no detectable t(14;18)-positive cells in any tissue sample. In the remaining 9 individuals (17 – 32 years) t(14;18)-positive cells could be detected: 5+/9 spleen tissues, 5+/9 tonsil tissue, 4+/9 peripheral blood, 2+/9 lymph node tissue, 1+/9 bone marrow. The 5 positive spleen tissue samples had a significant higher frequency of t(14;18) positive cells than observed in peripheral blood and all other tissue samples. In conclusion, expanded t(14;18)-positive cell clones can be detected circulating in the peripheral blood after the age of 10 years with an increasing prevalence and frequency until the age of 50. Among various lymphoid tissues obtained from individuals in the age of 17–32 years the highest frequency of t(14;18)-positive cells can be found in the spleen.

scholarly journals Molecular diagnosis angioimmunoblastic T-cell lymphoma

2019 ◽  
Vol 91 (7) ◽  
pp. 63-69
Author(s):  
N G Chernova ◽  
Y V Sidorova ◽  
S Y Smirnova ◽  
N V Ryzhikova ◽  
E E Nikulina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Tissue Samples ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Allele Specific

Aim: to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma. Materials and methods. Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used. Results. In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes. Conclusion. The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.

scholarly journals Translocation (14;18)-positive cells are present in the circulation of the majority of patients with localized (stage I and II) follicular non- Hodgkin's lymphoma

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2510-2516 ◽  
Author(s):  
AC Lambrechts ◽  
PE Hupkes ◽  
LC Dorssers ◽  
MB van't Veer
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Peripheral Blood ◽  
Hodgkin’S Lymphoma ◽  
Lymph Node Biopsy ◽  
Stage I ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Sensitive Polymerase Chain Reaction

Abstract Stage I and II follicular non-Hodgkin's lymphoma (NHL) is clinically defined as a localized disease. To study the possibility that this disease is in fact disseminated, we used the sensitive polymerase chain reaction (PCR) method using translocation (14;18) as marker. Samples from 21 patients who were clinically diagnosed with stage I or II follicular NHL were analyzed for the presence of t(14;18)-positive cells using PCR. We analyzed (1) the diagnostic lymph node biopsy and (2) the peripheral blood or bone marrow samples from these patients. Translocation (14;18) cells were detected in the diagnostic lymph node biopsies of 12 patients. In 9 of these patients, t(14;18)-positive cells were detected in peripheral blood and/or bone marrow samples at diagnosis and/or after therapy. Thus, in 75% of the follicular NHL patients carrying the t(14;18) as a marker for lymphoma cells, t(14;18)- positive cells were detected in peripheral blood and bone marrow at diagnosis and after therapy. Our results show that t(14;18)-positive cells can be detected in the circulation of patients with stage I and II follicular NHL, indicating that, although diagnosed as localized, the disease is disseminated.

scholarly journals Effects of Homozygosity of the nude (rnu) gene in an inbred strain of rats: Studies of lymphoid and non-lymphoid organs in different age groups of nude rats of LEW background at a stage in the gene transfer

1984 ◽  
Vol 18 (1) ◽  
pp. 7-14 ◽  
Author(s):  
H. P. Hougen ◽  
B. Klausen
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Genetic Background ◽  
Early Stage ◽  
Age Groups ◽  
Lymphoid Organs ◽  
Thymic Tissue ◽  
Nude Rats ◽  
Histological Appearance ◽  
Differential Counts

Several age groups of nude homozygous rnu/rnu and heterozygous rnu/+ rats of the same genetic background at an early stage of back-crossing (LEW/Mol) were compared as to body and organ weights, histological appearance and cell density of lymphoid organs, haematological values and differential counts of bone marrow and peripheral blood. No thymic tissue was found in the nude animals. 7-week-old nudes were smaller than control animals and had relatively larger non-lymphoid organs and cell-depleted peripheral lymphoid organs. Other age groups showed little difference. Peripheral blood of nude rats showed no signs of lymphopaenia in contrast with the findings in nude mice. The number of thoracic duct lymphocytes was, however, significantly smaller in all age groups of the nude rats, and the bone marrow tended to contain fewer lymphocytes.

BH3 Profiling Demonstrates Decreased Mitochondrial Priming for Apoptosis In Primary CLL Cells Exposed to Stroma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 692-692
Author(s):  
Matthew S. Davids ◽  
Jennifer R. Brown ◽  
Adrian Wiestner ◽  
Anthony G. Letai
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cell Viability ◽  
Cell Population ◽  
Peripheral Blood ◽  
Malignant Cells ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Bh3 Domain ◽  
Cells Cultured

Abstract Abstract 692 Treatments for chronic lymphocytic leukemia (CLL) often kill malignant cells in the peripheral blood, but the disease inevitably relapses in the lymph nodes or bone marrow. BH3 profiling was developed in our laboratory to assess the degree to which malignant cells are primed to undergo apoptosis by the mitochondrial pathway, and to identify the anti-apoptotic proteins on which these cells depend for their survival. We hypothesized that BH3 profiling can help elucidate mechanisms underlying stromal-mediated resistance to the BH3-mimetic ABT-737 in CLL. BH3 profiling was performed by exposing malignant CD19+ B cells from 15 CLL patients to a panel of BH3-domain peptides, and the cell death induced was quantified by JC-1 based FACS to assess mitochondrial outer membrane permeabilization, as previously described (Ryan et al., PNAS 2010). To simulate lymph node and bone marrow microenvironments, we co-cultured CLL cells from a subset of these patients for 24 hours in the presence of IL-4 with CD154+ fibroblasts and with HS5 cells, respectively, and then repeated BH3 profiling. The status of the chemokine receptor CXCR4, which can serve as a marker for the residence of CLL cells in stromal microenvironments, was also evaluated by FACS. Additional co-culture experiments were done in the presence or absence of ABT-737 at 100 nM, and CLL cell viability was assessed at 24 hours by Annexin-PI. We also performed BH3 profiling on 7 additional CLL patients with matched peripheral blood, lymph node, and bone marrow samples. Circulating malignant CLL cells were highly primed to undergo apoptosis, and their survival was mainly dependent on Bcl-2, and to a lesser degree Mcl-1. CXCR4 decreased on CLL cells co-cultured for 24 hours with CD154+ fibroblasts (38.6%) compared to cells cultured with parental controls (76.3%) (p = 0.030), but did not decrease on cells cultured with HS5 cells (87.1%) (p > 0.05). When CLL cells were co-cultured with CD154+ fibroblasts in the presence of ABT-737, mean CLL cell viability by Annexin-PI increased to 85.1% compared to 31.8% (p < 0.001) in cells co-cultured with parental controls. BH3 profiling revealed that CD154+ fibroblast exposure led to decreased CLL cell mitochondrial depolarization in response to Bim, Noxa, Hrk, and particularly to ABT-737 (see figure). In contrast, CLL cells exposed to HS5 cells had unchanged CXCR4 status, but still had a decrease in apoptotic priming, which was observed in response to an even broader range of BH3-domain peptides, including Puma and Bmf. When gating on the whole CLL cell population, the pattern and degree of apoptotic priming was similar in matched peripheral blood, lymph node, and bone marrow biopsy samples from 7 additional patients. Interestingly, gating on CXCR4 status revealed heterogeneity in apoptotic priming in the different microenvironments, with a subset of patients showing that CXCR4- bone marrow-derived CLL cells were less primed than their CXCR4+ counterparts. Overall, BH3 profiling demonstrated that circulating primary CLL cells are highly primed to undergo apoptosis, and depend predominantly on the anti-apoptotic protein Bcl-2 for their survival. CLL cells co-cultured with lymph node-like stroma had decreased CXCR4 surface expression and became resistant to ABT-737. BH3 profiling demonstrated that this resistance was accompanied by decreased apoptotic priming in response to several BH3-domain peptides. An even broader decrease in apoptotic priming was observed in response to co-culture with a bone marrow-like microenvironment, apparently unrelated to changes in CXCR4 status. Matched peripheral blood, lymph node, and bone marrow CLL patient samples had similar BH3 profiles overall, but some patients showed decreased apoptotic priming in CXCR4- CLL cells, which likely represent the true bone marrow resident CLL cell population. This heterogeneity in mitochondrial priming may help to explain some of the resistance to therapy observed in bone marrow and lymph nodes as compared to peripheral blood. Disclosures: Letai: Eutropics Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Gene expression of one important microRNA in blood and tissue samples of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Naghmeh Emami ◽  
Naghmeh Bahrami ◽  
Masoumeh Mirzaei ◽  
Abdolreza Mohamadnia
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Peripheral Blood ◽  
Expression Level ◽  
P Value ◽  
Healthy Individuals ◽  
Tissue Samples

Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most common oral malignancies, which accounts for 80-90% of malignant neoplasms of the oral cavity. MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by targeting mRNAs. Materials and Methods: In this case-control study, 40 patients with oral squamous cell carcinoma and 40 healthy individuals as control were studied. Blood samples were collected from both groups. Also, 30 cancer tissue samples and 30 healthy tissue samples were prepared and evaluated. RNA was extracted from collected peripheral blood and tissue samples and evaluated for the expression level of miR-494 via real-time PCR technique. P. value values<0.05 were considered statistically significant. Results: The expression level of miR-494 in serum (peripheral blood) of patients with oral squa- mous cell carcinoma increased by 1.12 fold (P-value<0.001) compared with healthy individuals. Also, the expression level of miR-494 in samples of oral squamous cell carcinoma infected tissue showed a 1.28-fold increase compared to healthy tissue. Conclusion: The results of this study indicate an increase in the expression level (up-regula- tion) of miR-494 in oral squamous cell carcinoma. This biomarker can be used in screening and early detection of oral squamous cell carcinoma.

Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1063-1069 ◽  
Author(s):  
Luciana Teofili ◽  
Anna Laura Di Febo ◽  
Francesco Pierconti ◽  
Nicola Maggiano ◽  
Maurizio Bendandi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hodgkin Disease ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Bone Marrow Biopsies ◽  
Barr Virus ◽  
Hepatocyte Growth

Abstract The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus–positive (EBV+) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF+. These results were independent of the EBV infection. Interestingly, several HGF+ dendritic-reticulum cells were found scattered around c-MET+ RS cells. The mean ± SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 ± 91 (95% confidence interval [CI], 1221-1585) and 1497 ± 242 pg/mL (95% CI, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 ± 28 pg/mL; 95% CI, 600-721; and P &lt; .001 for both groups of patients) and of HD patients in remission (616 ± 49 pg/mL; 95% CI, 517-714; andP &lt; .001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P = .014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of RS cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.

scholarly journals Some Factors Involved in the Effect of X-Irradiation on the Phosphatase Activity of Hematopoietic Tissues

Blood ◽  
1959 ◽  
Vol 14 (10) ◽  
pp. 1128-1136 ◽  
Author(s):  
EDWIN M. UYEKI ◽  
PAUL R. SALERNO
Keyword(s):  
Bone Marrow ◽  
Enzyme Activity ◽  
Peripheral Blood ◽  
Adenosine Triphosphatase ◽  
Lymphoid Tissues ◽  
X Ray ◽  
Adenosine Triphosphatase Activity ◽  
Assay Medium ◽  
X Irradiation ◽  
Total Body

Abstract Factors which modify lymphoid distribution of tissues were found to modify the adenosine triphosphatase activity of these tissues. Starvation or cortisone injection, which produces destructive changes in lymphoid tissues, was found to increase the enzyme activity of spleen and thymus tissues. The greater increment of enzyme activity of the thymus as compared to that of the spleen was correlated with its normally higher content of lymphoid tissue. The increase in adenosine triphosphatase activity of hematopoietic tissues appears to be associated with the type of cells present in the assay medium. With respect to peripheral blood leukocytes of the rat, the cell type is confined largely to lymphocytes and granulocytes. The increase in adenosine triphosphatase activity of the leukocytes after total-body x-ray was seen to parallel the increase in granulocytes present in the assay medium. The ratio of granulocytes to lymphocytes is not appreciably altered in dog peripheral blood after exposure to total-body x-ray; the adenosine triphosphatase activity similarly was not significantly altered. After total-body x-ray (390 r and 780 r), cells isolated from the rat bone marrow displayed a fivefold increase in adenosine triphosphatase activity. This increase was seen to correspond with an increase in the ratio of segmented leukocytes and reticuloendothelial cells and a decrease in the immature forms of the erythroid and myeloid cells. The heterogeneous cell mixtures used for our assay procedures permit the observation that total-body x-irradiation results in an increased enzyme activity of the isolated cells of the peripheral blood, bone marrow and spleen tissue of the rat. The increased enzyme activity was associated with the increased ratio of cells with high enzyme activity present in the assay medium.

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