Transplantation of Large Granular Lymphocyte Leukemia in Congenitally Athymic Rats

1992 ◽  
Vol 29 (3) ◽  
pp. 216-222 ◽  
Author(s):  
P. C. Stromberg ◽  
T. J. Rosol ◽  
I. S. Grants ◽  
L. E. Mezza
Keyword(s):  
Tumor Cells ◽  
Hemolytic Anemia ◽  
Cell Function ◽  
Leukemia Cell ◽  
Large Granular Lymphocyte ◽  
White Pulp ◽  
Spleen Cells ◽  
Cell Width ◽  
Large Granular Lymphocyte Leukemia ◽  
F344 Rats

Twenty-two congenitally athymic nude ( rnu/rnu) rats were transplanted with large granular lymphocyte leukemia derived from F344 rats and then compared with ten similar rats inoculated with a suspension of normal F344 rat spleen cells. The normal spleen cells and tumor cells from a spontaneous, naturally occurring leukemia did not grow or cause clinical disease in any of the rats. All rats inoculated with a serially passaged leukemia cell inoculum had local growth at the inoculation site that spread widely and resulted in progressive tumor growth. Death occurred between 16 and 38 days after inoculation. The 22 rats that received passaged tumor cells developed leukemia and splenomegaly. Spleens were diffusely infiltrated by tumor cells and had severe depletion of lymphocytes in the white pulp. Leukemic rats were thrombocytopenic and had hemolytic anemia characterized by increased osmotic fragility, red cell width, and many nucleated erythrocytes. The disease syndrome appears similar to that of F344 rats transplanted with the same inoculum. Because the host rats lacked T cells, it is concluded that the hemolytic anemia and thrombocytopenia that develop in transplanted rats are independent of T cell function.

Spleen Cell Population Changes and Hemolytic Anemia in F344 Rats with Large Granular Lymphocyte Leukemia

1990 ◽  
Vol 27 (6) ◽  
pp. 397-403 ◽  
Author(s):  
P. C. Stromberg ◽  
G. J. Kociba ◽  
I. S. Grants ◽  
G. S. Krakowka ◽  
J. J. Rinehart ◽  
...  
Keyword(s):  
Spleen Cell ◽  
Hemolytic Anemia ◽  
Cell Population ◽  
Large Granular Lymphocyte ◽  
Population Changes ◽  
Large Granular Lymphocyte Leukemia ◽  
F344 Rats

scholarly journals Impact of large granular lymphocyte leukemia on blood DNA methylation and epigenetic clock modeling in Fischer 344 rats

2021 ◽  
Author(s):  
Giovanni E Finesso ◽  
Ross A McDevitt ◽  
Roshni Roy ◽  
Lauren R Brinster ◽  
Andrea Di Francesco ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Granular Lymphocyte ◽  
Epigenetic Clock ◽  
Selection Probability ◽  
Large Granular Lymphocyte Leukemia ◽  
Reduced Representation ◽  
Fischer 344 ◽  
Adverse Health Outcomes ◽  
Epigenetic Age ◽  
F344 Rats

Abstract Age-dependent differences in methylation at specific cytosine-guanosine sites (CpGs) have been used in “epigenetic clock” formulas to predict age. Deviations of epigenetic age from chronological age are informative of health status and are associated with adverse health outcomes, including mortality. In most cases, epigenetic clocks are performed on methylation from DNA extracted from circulating blood cells. However, the effect of neoplastic cells in the circulation on estimation and interpretation of epigenetic clocks is not well understood. Here, we explored this using Fischer 344 (F344) rats, a strain that often develops large granular lymphocyte leukemia (LGL). We found clear histological markers of LGL pathology in the spleens and livers of 27 out of 61 rats aged 17-27 months. We assessed DNA methylation by reduced representation bisulfite sequencing with coverage of 3 million cytosine residues. Although LGL broadly increased DNA methylation variability, it did not change epigenetic aging. Despite this, inclusion of rats with LGL in clock training sets significantly altered predictor selection probability at 83 of 121 commonly utilized CpGs. Furthermore, models trained on rat samples that included individuals with LGL had greater absolute age error than those trained exclusively on LGL-free rats (39% increase; p<0.0001). We conclude that the epigenetic signals for aging and LGL are distinct, such that LGL assessment is not necessary for valid measures of epigenetic age in F344 rats. The precision and architecture of constructed epigenetic clock formulas, however, can be influenced by the presence of neoplastic hematopoietic cells in training set populations.

scholarly journals Serial Syngeneic Transplantation of Large Granular Lymphocyte Leukemia in F344 Rats

1990 ◽  
Vol 27 (6) ◽  
pp. 404-410 ◽  
Author(s):  
P. C. Stromberg ◽  
I. S. Grants ◽  
G. J. Kociba ◽  
G. S. Krakowka ◽  
L. E. Mezza
Keyword(s):  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia ◽  
F344 Rats

scholarly journals Cytokine-Induced Memory-Like NK Cells with High Reactivity against Acute Leukemia Blasts and Solid Tumor Cells Suitable for Adoptive Immunotherapy Approaches

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1577
Author(s):  
Matteo Tanzi ◽  
Michela Consonni ◽  
Michela Falco ◽  
Federica Ferulli ◽  
Enrica Montini ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Lymphoid Leukemia ◽  
Hematopoietic Stem ◽  
Solid Malignancies

The limited efficacy of Natural Killer (NK) cell-based immunotherapy results in part from the suboptimal expansion and persistence of the infused cells. Recent reports suggest that the generation of NK cells with memory-like properties upon in vitro activation with defined cytokines might be an effective way of ensuring long-lasting NK cell function in vivo. Here, we demonstrate that activation with IL-12, IL-15 and IL-18 followed by a one-week culture with optimal doses of Interleukin (IL-2) and IL-15 generates substantial numbers of memory-like NK cells able to persist for at least three weeks when injected into NOD scid gamma (NSG) mice. This approach induces haploidentical donor-derived memory-like NK cells that are highly lytic against patients’ myeloid or lymphoid leukemia blasts, independent of the presence of alloreactive cell populations in the donor and with negligible reactivity against patients’ non-malignant cells. Memory-like NK cells able to lyse autologous tumor cells can also be generated from patients with solid malignancies. The anti-tumor activity of allogenic and autologous memory-like NK cells is significantly greater than that displayed by NK cells stimulated overnight with IL-2, supporting their potential therapeutic value both in patients affected by high-risk acute leukemia after haploidentical hematopoietic stem cell transplantation and in patients with advanced solid malignancies.

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