scholarly journals A case of chronic lymphocytic leukemia with properties characteristic of natural killer cells

Blood ◽  
1983 ◽  
Vol 61 (5) ◽  
pp. 940-948 ◽  
Author(s):  
K Itoh ◽  
K Tsuchikawa ◽  
T Awataguchi ◽  
K Shiiba ◽  
K Kumagai
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Surface Markers ◽  
T Antigens ◽  
Homogeneous Population

Abstract A case of chronic lymphocytic leukemia that consisted of a homogeneous population of cells that had properties similar to those described for natural killer (NK) cells is presented. These leukemic cells had a morphology of large granular lymphocytes (LGL) and receptors for sheep erythrocytes (ER) and for the Fc portion of IgG (Fc gamma-R). They expressed pan-T antigens OKT3 and Leu-4, but neither helper/inducer T- cell differentiation antigens OKT4 and Leu-3a nor cytotoxic/suppressor T-antigens OKT8 and Leu-2a. HNK 1 antigen, which can be expressed on human NK cells, could be detected on almost all leukemic cells (LGL), whereas a myeloid differentiation antigen, OKM1, which can be expressed on macrophages, granulocytes, and NK cells, was not detected. Thus, it was concluded that the leukemia cells had a characteristic profile of the surface markers: ER+, Fc gamma-R+, HNK-1+, OKT3+, Leu-4+, OKT4-, OKT8-, Leu-3a, Leu-2a, and OKM1-. Although freshly isolated leukemic cells showed no cytotoxicity on NK targets, after incubation at 37 degrees C, the cells did show a potent cytotoxicity on targets of erythroleukemic cell, T cell, and monocyte (but not B cell) origins. When the cells were incubated at 37 degrees C, interferon (IFN gamma) was spontaneously produced in the culture fluids. Treatment with anti- HNK-1 and complement completely abrogated expression of NK activity and interferon production of the patient's lymphocytes in culture. These characteristic features of surface markers and functions strongly suggest the possibility that the leukemia cells of this case are of NK cell origin. The relationship between this case and chronic lymphocytic leukemia of T-cell origin is discussed.

scholarly journals A case of chronic lymphocytic leukemia with properties characteristic of natural killer cells

Blood ◽  
1983 ◽  
Vol 61 (5) ◽  
pp. 940-948
Author(s):  
K Itoh ◽  
K Tsuchikawa ◽  
T Awataguchi ◽  
K Shiiba ◽  
K Kumagai
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Surface Markers ◽  
T Antigens ◽  
Homogeneous Population

A case of chronic lymphocytic leukemia that consisted of a homogeneous population of cells that had properties similar to those described for natural killer (NK) cells is presented. These leukemic cells had a morphology of large granular lymphocytes (LGL) and receptors for sheep erythrocytes (ER) and for the Fc portion of IgG (Fc gamma-R). They expressed pan-T antigens OKT3 and Leu-4, but neither helper/inducer T- cell differentiation antigens OKT4 and Leu-3a nor cytotoxic/suppressor T-antigens OKT8 and Leu-2a. HNK 1 antigen, which can be expressed on human NK cells, could be detected on almost all leukemic cells (LGL), whereas a myeloid differentiation antigen, OKM1, which can be expressed on macrophages, granulocytes, and NK cells, was not detected. Thus, it was concluded that the leukemia cells had a characteristic profile of the surface markers: ER+, Fc gamma-R+, HNK-1+, OKT3+, Leu-4+, OKT4-, OKT8-, Leu-3a, Leu-2a, and OKM1-. Although freshly isolated leukemic cells showed no cytotoxicity on NK targets, after incubation at 37 degrees C, the cells did show a potent cytotoxicity on targets of erythroleukemic cell, T cell, and monocyte (but not B cell) origins. When the cells were incubated at 37 degrees C, interferon (IFN gamma) was spontaneously produced in the culture fluids. Treatment with anti- HNK-1 and complement completely abrogated expression of NK activity and interferon production of the patient's lymphocytes in culture. These characteristic features of surface markers and functions strongly suggest the possibility that the leukemia cells of this case are of NK cell origin. The relationship between this case and chronic lymphocytic leukemia of T-cell origin is discussed.

scholarly journals Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes’ army

2019 ◽  
Vol 5 (10) ◽  
pp. FSO425
Author(s):  
Ricardo García-Muñoz ◽  
María-Josefa Nájera ◽  
Jesús Feliu ◽  
Judith Antón-Remírez ◽  
Enrique Ramalle-Gómara ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Killer Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells

Aim: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. Patients & methods: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. Results: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. Conclusion: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

scholarly journals Chronic lymphocytic leukemia cells induce defective LFA-1–directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide

Blood ◽  
2013 ◽  
Vol 121 (14) ◽  
pp. 2704-2714 ◽  
Author(s):  
Alan G. Ramsay ◽  
Rachel Evans ◽  
Shahryar Kiaii ◽  
Lena Svensson ◽  
Nancy Hogg ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Motility ◽  
Rho Gtpase ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Key Points ◽  
Gtpase Activation ◽  
Activation Signaling

Key Points CLL cells induce defects in T-cell LFA-1–mediated migration by altering Rho GTPase activation signaling, downregulating RhoA and Rac1, and upregulating Cdc42. Lenalidomide repairs these T-cell defects by restoring normal Rho GTPase activation signaling.

scholarly journals Heterogeneity of the response of chronic lymphocytic leukemia cells to phorbol ester

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1082-1088 ◽  
Author(s):  
J Okamura ◽  
EW Gelfand ◽  
M Letarte
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phorbol Ester ◽  
Mixed Lymphocyte Reaction ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Phenotypic Markers ◽  
Tumor Promotor ◽  
Bright Surface

Abstract The ability of the tumor promotor 12–0-tetradecanoylphorbol 13-acetate (TPA) to induce differentiation of leukemic cells was studied in 10 cases of chronic lymphocytic leukemia (CLL). An increase in modal volume and an enhancement of the capacity of te leukemic cells to stimulate in mixed lymphocyte reaction (MLR) was seen in the majority of cases. A significant increase in Ia expression was observed upon culture of leukemic cells with TPA in 6 of the 10 cases; 5 of these cases also showed an induction of cytoplasmic IgM production. Correlations between the phenotypic markers of the leukemic cells and their ability to respond to TPA were evaluated. CLL cells with low amounts to surface Ig. a volume less than or equal to 165 fl. and relatively low la expression responded well to TPA. Cells with bright surface Ig. a volume greater than or equal to 178 fl. and elevated amounts of Ia responded poorly to TPA. These results suggest that differences in the response of B leukemic cells to TPA reflect the underlying heterogeneity of the leukemic cells and might be correlated with their stage of maturation.

Superagonistic Anti-CD28 Antibody TGN1412 as a Potential Immunotherapeutic for the Treatment of B Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2519-2519 ◽  
Author(s):  
Chia-Huey Lin ◽  
Thomas Kerkau ◽  
Christine Guntermann ◽  
Martin Trischler ◽  
Niklas Beyersdorf ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Activation Markers ◽  
Cell Chronic Lymphocytic Leukemia

Abstract B cell chronic lymphocytic leukemia (B-CLL) is characterised by an accumulation of malignant B cells, and impaired humoral and cellular immune responses. Evasion strategies of leukemic cells appear to involve down-regulation of co-stimulatory molecules as well as increased resistance to apoptosis. Here we provide data supporting a novel concept to treat B-CLL with a humanized, superagonistic monoclonal antibody specific for CD28 (TGN1412). Superagonistic anti-CD28 antibodies have been shown to activate human T cells in vitro without requirement for engagement of the T cell antigen receptor (Luhder et al., J. Exp. Med. 2003. 197(8):955–66). Indicative of their activation, TGN1412-triggered T cells from healthy donors upregulate, among other activation markers, CD40L, that has been reported to promote anti-leukemic effects when ectopically expressed on B-CLL cells (Wierda et al., Blood. 2000. 96 (9): 2917–2924). In this report, the responses of PBMCs from B-CLL patients to soluble TGN1412 were examined. We show that in a dose-dependent fashion, polyclonal T cell activation was induced by TGN1412 including proliferation, cytokine production and induction of activation markers such as CD25, CD71, CD134 (Ox40), CTLA-4 (CD152) and CD154 (CD40L). Significantly, modulation of malignant B-CLL cells was also observed. MHC class II molecules (HLA-DR), CD95 and the co-stimulatory molecules CD80 and CD86, but not the proliferation marker Ki-67, were strongly up-regulated upon TGN1412 stimulation. These data suggested that improved antigen-presenting functions of B-CLL cells were induced by TGN1412. Accordingly, preliminary data indicate that B-CLL cells isolated from TGN1412 stimulated cultures induced enhanced proliferation of both allogeneic and autologous T cells, and importantly, TGN1412 activated T cells exhibited enhanced CTL-activity against B-CLL cells. In conclusion, our data suggest that TGN1412 induces polyclonal T cell expansion and activation as well as increased APC function of B-CLL cells. They imply that TGN1412 may have future therapeutic benefit for B-CLL patients.

scholarly journals Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells

2016 ◽  
Vol 7 ◽  
Author(s):  
Diego Sánchez-Martínez ◽  
Pilar M. Lanuza ◽  
Natalia Gómez ◽  
Aura Muntasell ◽  
Elisa Cisneros ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cells ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals Blinatumomab induces autologous T-cell killing of chronic lymphocytic leukemia cells

Haematologica ◽  
2013 ◽  
Vol 98 (12) ◽  
pp. 1930-1938 ◽  
Author(s):  
R. Wong ◽  
C. Pepper ◽  
P. Brennan ◽  
D. Nagorsen ◽  
S. Man ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Killing ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells

scholarly journals Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Target Cells ◽  
Nk Cell Activity

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.

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