The Local Sanarelli-Shwartzman Phenomenon in Rats Induced by Human Leukaemic Cells

1973 ◽  
Vol 29 (02) ◽  
pp. 353-362
Author(s):  
J Lisiewicz ◽  
A Pituch ◽  
J. A Litwin

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.

Author(s):  
P H Whiting ◽  
D J King ◽  
A Ireland ◽  
M A Ratcliffe ◽  
A A Dawson

The activity of the lysosomal hydrolase N-acetyl-β-d-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1–3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine β2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.


1976 ◽  
Vol 32 (4) ◽  
pp. 609-616 ◽  
Author(s):  
I. E. Fortuny ◽  
D. C. Hadlock ◽  
B. J. Kennedy ◽  
A. Theologides ◽  
J. McCullough

2020 ◽  
pp. 5302-5310
Author(s):  
Clive S. Zent ◽  
Aaron Polliack

Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma is the most prevalent lymphoid neoplasm in Europe and North America. The ‘cell of origin’ is a mature B lymphocyte with a rearranged immunoglobulin gene. CLL cells express modest amounts of surface immunoglobulin, and are characterized by defective apoptosis. The cause of CLL is unknown. Most patients show no specific clinical features of disease and are diagnosed during evaluation of an incidental finding of peripheral blood lymphocytosis, lymphadenopathy, or splenomegaly. A small percentage of patients (<10%) present with symptomatic disease resulting from (1) tissue accumulation of lymphocytes such as disfiguring lymphadenopathy, splenomegaly with abdominal discomfort, profound fatigue, drenching night sweats, weight loss, and fever; or (2) manifestations of marrow failure with cytopenias including anaemia and thrombocytopenia. All CLL patients have an increased risk of infection, autoimmune cytopenias, and second haematological (e.g. diffuse large B-cell lymphoma) and nonhaematological malignancies. Diagnosis is usually made by analysis of the immunophenotype of the monoclonal circulating cells in the peripheral blood. In patients with the small lymphocytic variant of CLL without a detectable circulating monoclonal B-cell population, the diagnosis is made using tissue from the bone marrow, lymph nodes, or spleen. Treatment—there is no standard curative therapy and patients should not be treated until they have progressive and symptomatic disease or develop anaemia or thrombocytopenia due to bone marrow failure. If a decision is made to treat, then the best initial treatment should be given, based on evaluation of the patient’s disease characteristics with specific attention to the integrity of TP53 (coding for p53) and patient fitness.


2020 ◽  
Vol 123 (2) ◽  
pp. 240-251 ◽  
Author(s):  
Eric P. Allain ◽  
Michèle Rouleau ◽  
Katrina Vanura ◽  
Sophie Tremblay ◽  
Joanie Vaillancourt ◽  
...  

Abstract Background High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents. Methods Functional enzymatic assays and patients’ plasma samples were analysed by mass-spectrometry to evaluate drug inactivation by UGT2B17. Cytotoxicity assays and RNA sequencing were used to assess drug response and transcriptome changes associated with high UGT2B17 levels. Results High UGT2B17 in B-cell models led to reduced sensitivity to fludarabine, ibrutinib and idelalisib. UGT2B17 expression in leukaemic cells involved a non-canonical promoter and was induced by short-term treatment with these anti-leukaemics. Glucuronides of both fludarabine and ibrutinib were detected in CLL patients on respective treatment, however UGT2B17 conjugated fludarabine but not ibrutinib. AMP-activated protein kinase emerges as a pathway associated with high UGT2B17 in fludarabine-treated patients and drug-treated cell models. The expression changes linked to UGT2B17 exposed nuclear factor kappa B as a key regulatory hub. Conclusions Data imply that UGT2B17 represents a mechanism altering drug response in CLL through direct inactivation but would also involve additional mechanisms for drugs not inactivated by UGT2B17.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Martin Gauthier ◽  
Françoise Durrieu ◽  
Elodie Martin ◽  
Michael Peres ◽  
François Vergez ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4955-4955
Author(s):  
Jaroslaw Piszcz ◽  
Slawomir Ziarko ◽  
Janusz Kloczko ◽  
Piotr Radziwon ◽  
Eliza Blusiewicz ◽  
...  

Abstract Background: Endocannabinoids take part in physiology of neural and immune system. Last data showed that these compounds and their receptors play an important role in proliferation and apoptosis of different neoplastic cells. Cannabinoids were shown to increase the apoptosis in human neoplastic cells through a number of mechanisms including vanilloid receptors (Sanchez et al. 1998, Maccarone et al. 2000). The vanilloid receptor family of cation channels includes the capsaicin-sensitive, proton- and heat-activated vanilloid receptor type I (TRPV1). Furthermore Saunders et al. (2006) showed that TRPV1 are expressed on normal lymphocytes in human peripheral blood. Aims: The aim of our study was the assessment of receptor TRPV1 mRNA expression in the lymphocytes B derived from patients with newly diagnosed chronic lymphocytic leukaemia. Material and methods: The study group contains newly diagnosed, untreated adult patients with B-cell chronic lymphocytic leukaemia; 11 males and 10 females, aged from 46 to 74. The patients were in A-C stage according to Binet. We used 13 samples from healthy donors as a control group. The isolation of mononuclear cells from peripheral blood was carried out with the use of density centrifugation method. The resolution of mononuclear cell population to lymphocytes B subpopulation was done with negative isolation method utilizing magnetic microballs (Dynal). Total RNA was isolated from B-lymphatic cells of which 10ng was used in each reaction. Quantitative RT-PCR was carried out with the use of Light Cycler (Roche) and respective commercial kits. The nucleotides sequence of the studied receptor and parameters of the amplification process were based on method previously described by Qiao et al (2003). We used house keeping gene hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) (G6PDH) as a reference gene. Amplification product was sequenced by ABI PRISM (Applied Biosystem). All results are presented as a mean concentration ratio of TRPV1 to G6PDH mRNA ± standard error. Statistical analysis was performed using Shapiro-Wilk, non parametric U Mann-Whitney Tests. Results: We found that concentration ratio of studied transcript was significantly lower in the study group in comparison to the control group (0,048± 0,012 vs. 106,836± 40,215 respectively. We found no differences between the subgroups irrespectively of gender, age, stage of the disease and some prognostic factors (LDH, lymphocyte doubling time, β2-microglobulin). Conclusions: The results confirm the existence of vanilloid receptors on the lymphocytes B of healthy individuals and for the first time show presence of this type of receptors in CLL group. The lower level of TRPV1 transcripts in the group of patient may suggests their potential role in the process of leukemic transformation. Thus the effect of endocannabinoids through this receptor may be altered in CLL. However, further studies are required to elucidate the nature of relationship between this type of receptor and neoplastic development of CLL.


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