Methylation of c-myc gene changes in human lymphoproliferative diseases

1987 ◽  
Vol 7 (8) ◽  
pp. 637-643 ◽  
Author(s):  
Yasahiro Deguchi ◽  
Shigeru Negoro ◽  
Susumu Kishimoto
Keyword(s):  
Mononuclear Cells ◽  
Normal Subjects ◽  
Lymphocytic Leukemia ◽  
Actin Gene ◽  
Lymphoproliferative Diseases ◽  
Peripheral Blood Mononuclear ◽  
Methylation Sensitive Restriction Enzyme ◽  
Myc Gene ◽  
The Relationship ◽  
Age And Sex

The degree of methylation at the c-myc proto-oncogene was found to change in human lymphoproliferative diseases, when examined using a methylation-sensitive restriction enzyme. In peripheral blood mononuclear cells (PBMC) c-myc DNA showed hypomethylation in human lymphoproliferative diseases, in comparison to normal subjects matched in age and sex. In cases of chronic lymphocytic leukemia (CLL), the change was amplified in the crisis. When the DNA was examined at the actin gene, no significant change was observed. The results suggest that the change in c-myc proto-oncogene methylation might become an important clue in understanding the relationship between levels of gene expression and methylation in human lymphoproliferative diseases.

scholarly journals Distribution of complement receptors on human normal and malignant mononuclear cells

Blood ◽  
1980 ◽  
Vol 56 (5) ◽  
pp. 792-797
Author(s):  
RB Slease ◽  
JE Gadek ◽  
MM Frank ◽  
I Scher
Keyword(s):  
Fluorescence Intensity ◽  
Mononuclear Cells ◽  
Human Subjects ◽  
Normal Subjects ◽  
Cell Types ◽  
Lymphocytic Leukemia ◽  
Homogeneous Distribution ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Heterogeneous Distribution

Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence- activated cell sorter (FACS). FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. Analyses in which either monocytes or B lymphcoytes were excluded from consideration demonstrated that both these cell types were labeled by the FI-C3b with a heterogeneous distribution of fluorescence intensity, indicating either heterogeneity of CR density or variable avidity of individual CR for the FI-C3b. FACS profiles of PBM ( < 5% monocytes) from 14 of 15 patients with CLL showed a homogeneous distribution of very low fluorescence intensity, with > 60% of the cells being slightly more fluorescent than unlabeled controls. This low, homogeneous distribution of fluorescence is strikingly similar to profiles of CLL cells labeled with anti-Ig reagents and suggests homogeneity of low CR density and/or avidity. Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. Homogeneity of FI-C3b binding to CLL, LCL, and HCL cells further supports the concept for a clonal origin for these disorders.

scholarly journals Distribution of complement receptors on human normal and malignant mononuclear cells

Blood ◽  
1980 ◽  
Vol 56 (5) ◽  
pp. 792-797 ◽  
Author(s):  
RB Slease ◽  
JE Gadek ◽  
MM Frank ◽  
I Scher
Keyword(s):  
Fluorescence Intensity ◽  
Mononuclear Cells ◽  
Human Subjects ◽  
Normal Subjects ◽  
Cell Types ◽  
Lymphocytic Leukemia ◽  
Homogeneous Distribution ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Heterogeneous Distribution

Abstract Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence- activated cell sorter (FACS). FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. Analyses in which either monocytes or B lymphcoytes were excluded from consideration demonstrated that both these cell types were labeled by the FI-C3b with a heterogeneous distribution of fluorescence intensity, indicating either heterogeneity of CR density or variable avidity of individual CR for the FI-C3b. FACS profiles of PBM ( < 5% monocytes) from 14 of 15 patients with CLL showed a homogeneous distribution of very low fluorescence intensity, with > 60% of the cells being slightly more fluorescent than unlabeled controls. This low, homogeneous distribution of fluorescence is strikingly similar to profiles of CLL cells labeled with anti-Ig reagents and suggests homogeneity of low CR density and/or avidity. Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. Homogeneity of FI-C3b binding to CLL, LCL, and HCL cells further supports the concept for a clonal origin for these disorders.

scholarly journals Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex [see comments]

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1770-1780 ◽  
Author(s):  
M Massaia ◽  
A Bianchi ◽  
C Attisano ◽  
S Peola ◽  
V Redoglia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Normal Subjects ◽  
Cross Linking ◽  
Peripheral Blood Mononuclear ◽  
Hla Dr ◽  
Lower Ratio

Abstract Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte- independent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P less than .001), soluble OKT3 (CD3) (P = .01), and immobilized OKT3 MoAbs (P = .01). On purification of T cells, MM responses were still defective to soluble T11(2) + T11(3) (CD2) MoAbs (P = .004), phorbol myristate acetate (PMA) plus ionomycin (P less than .001), but significantly higher to plastic-immobilized OKT3 (P = .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+ HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+ HLA-DR+ cells had significantly higher responses to immobilized OKT3 (P less than .001), but lower responses to T11(2) plus T11(3) (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8+ HLA-DR+ cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P less than .05) and CD8 (P less than .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+ lymphocytes.

Monoglycerides induce apoptosis in human leukemic cells while sparing normal peripheral blood mononuclear cells

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 292-294 ◽  
Author(s):  
Fabianne Philippoussis ◽  
Chantal Arguin ◽  
Véronique Mateo ◽  
Ann-Muriel Steff ◽  
Patrice Hugo
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Major Drawback ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Blood Mononuclear Cells

Abstract A major drawback of the current antineoplastic treatments is their lack of specificity toward cancer cells, because they are most often cytotoxic to normal cells, thus creating related side effects. Hence, the identification of new apoptosis-inducing agents, specifically targeting malignant cells while sparing their normal counterparts, is of crucial interest. We show here that monoglycerides, a family of lipids consisting of a single fatty acid attached to a glycerol backbone, induce cell death in several human leukemic cell lines. Importantly, treatment of primary leukemic cells, obtained from B-cell chronic lymphocytic leukemia patients, resulted in rapid apoptosis. In striking contrast, resting or activated human peripheral blood mononuclear cells from healthy individuals were resistant to the same treatment. Therefore, these compounds could represent potential antileukemic drugs or could allow for the design of novel therapeutic agents applied to leukemia.

BTK Inhibitors, Irrespective of ITK Inhibition, Increase Efficacy of a CD19/CD3 Bispecific Antibody in CLL

Blood ◽  
2021 ◽  
Author(s):  
Maissa Mhibik ◽  
Erika M. Gaglione ◽  
David Eik ◽  
Ellen K Kendall ◽  
Amy Blackburn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Kinase Inhibitors ◽  
Bispecific Antibody ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear

Bruton Tyrosine Kinase inhibitors (BTKis) are a preferred treatment for patients with chronic lymphocytic leukemia (CLL). Indefinite therapy with BTKis, while effective, presents clinical challenges. Combination therapy can deepen responses, shorten treatment duration, and possibly prevent or overcome drug resistance. We previously reported on a CD19/CD3 bispecific antibody (bsAb) that recruits autologous T cell cytotoxicity against CLL cells in vitro. Compared to observations with samples from treatment-naïve patients, T cells from patients being treated with ibrutinib expanded more rapidly and exerted superior cytotoxic activity in response to the bsAb. In addition to BTK, ibrutinib also inhibits IL2 inducible T cell Kinase (ITK). In contrast, acalabrutinib, does not inhibit ITK. Whether ITK inhibition contributes to the observed immune effects is unknown. To better understand how BTKis modulate T-cell function and cytotoxic activity, we cultured peripheral blood mononuclear cells (PBMCs) from BTKi-naive, and ibrutinib- or acalabrutinib-treated CLL patients with CD19/CD3 bsAb in vitro. T-cell expansion, activation, differentiation, and cytotoxicity were increased in PBMCs from patients on treatment with either BTKi compared to that observed for BKTi-naïve patients. BTKi therapy transcriptionally downregulated immunosuppressive effectors expressed by CLL cells, including CTLA-4 and CD200. CTLA-4 blockade with ipilimumab in vitro increased the cytotoxic activity of the bsAb in BTKi-naïve but not BTKi-treated PBMCS. Taken together, BTKis enhance bsAb induced cytotoxicity by relieving T cells of immunosuppressive restraints imposed by CLL cells. The benefit of combining bsAb immunotherapy with BTKis needs to be confirmed in clinical trials.

Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2045-2048 ◽  
Author(s):  
Chiara Azzari ◽  
Massimo Resti ◽  
Maria Moriondo ◽  
Roberto Ferrari ◽  
Paolo Lionetti ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Hcv Rna ◽  
Cell Infection ◽  
Transmitted Infection ◽  
Peripheral Blood Mononuclear ◽  
Maternal Peripheral Blood ◽  
Hcv Transmission ◽  
The Relationship

Abstract Infection of peripheral blood mononuclear cells (PBMNCs) has been demonstrated to be a crucial event in the vertical transmission of viruses, and it is known that hepatitis C virus (HCV) can infect PBMNCs. The relationship between vertical transmission of HCV and the presence of positive and negative strands of HCV-RNA in the PBMNCs of HCV-carrier mothers was investigated using reverse transcriptase–polymerase chain reaction (RT-PCR). During the study, 13 consecutive mothers who transmitted infection to their offspring and 53 consecutive mothers who did not were examined. The positive strand of HCV-RNA was identified in the PBMNCs of all mothers who transmitted the infection and in 13 of 53 mothers who did not (P &lt; 10−6). The HCV-RNA−strand was found in 5 of 13 mothers who transmitted the infection, and the strand was not found in the mothers who did not transmit the infection (P = .0001). Neither maternal PBMNC infection nor HCV transmission to the offspring was significantly related to the viral genotype or to the maternal viral load. These data show that maternal PBMNC infection by HCV and viral replicative activity in PBMNCs are important factors in the transmission of HCV from mother to child. The mechanism through which HCV infection of PBMNC favors vertical transmission of the virus is still incompletely understood.

scholarly journals Circulating immunoglobulin-secreting cells in patients with plasma cell dyscrasia

Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 590-594 ◽  
Author(s):  
K Shimizu ◽  
T Murate ◽  
A Kunii
Keyword(s):  
Plasma Cell ◽  
Mononuclear Cells ◽  
Clinical Stage ◽  
Laboratory Data ◽  
Plaque Assay ◽  
Plasma Cell Dyscrasia ◽  
Healthy Individuals ◽  
Normal Range ◽  
Peripheral Blood Mononuclear ◽  
The Relationship

Abstract Immunoglobulin-secreting cells (ISC) in peripheral blood mononuclear cells (PBM) isolated from patients with plasma cell dyscrasia of various stages were studied using reverse hemolytic plaque assay. Normal healthy individuals contained 35 +/- 16 ISC/10(5) PBM. Aleukemic or subleukemic patients with overt myeloma contained 825 +/- 713 ISC, whereas leukemic patients contained 12,675 +/- 2520 ISC. Patients of premyelomatous stage, however, contained ISC/10(5) PBM of normal range. The relationship between ISC and clinical stage or laboratory data is discussed.

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