Reduced expression of cell cycle-associated genes in B lymphocytes purified from the peripheral blood of early-stage B chronic lymphocytic leukaemia patients

Abstract B-cell chronic lymphocytic leukaemia (B-CLL) is the most common leukaemia of adults in Western worls accounting for about 40% of leukemias in adults over the age of 65 years. Although, B-CLL cells can, under certain conditions, act as antigen presenting cell (APCs) they fail to generate an efficient anti-leukemic immune response. Dendritic cells (DCs) represent the most potent APCs and they are the only cell type capable of initiating a primary immune response. To asses a potential role of DCs compartment in insufficient anti-leukemic and anti-infectious immunity in B-CLL, we have analysed peripheral blood DCs subsets in 17 patients with an early stage B-CLL and 8 age matched controls by multi colour flow cytometry. Dendritic cells were identified by lack of B, T, NK and monocyte markers, HLA-DR expression and expression of CD11c and CD123 for myeloid and plasmacytoid DCs, respectively. We found a significant reduction of absolute plasmacytoid DCs counts in patients with B-CLL (average count = 49,4×106/L) when compared to healthy donors (average count = 111,3 ×106/L, p<0,05). Myeloid DCs counts were not different from healthy controls (average count = 192,7×106/L vs. 196,7×106/L p=NS). Number of plasmacytoid DCs decreased with B-CLL cells number. DC counts did not depend on CD38 or ZAP70 expression or immunoglobulin mutational status. Phenotypic analysis of circulating plasmacytoid and myeloid DCs showed low co-stimulation profile comparing to isotype controls. Thus, the depletion of pDCs in B-CLL could represent a mechanism contributing to the poor anti-leukemic immune responses in B-CLL and/or to immune deficiency in CLL patients.

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Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia

Journal of Clinical Pathology ◽

10.1136/jcp.2008.060152 ◽

2008 ◽

Vol 61 (11) ◽

pp. 1214-1219 ◽

Cited By ~ 38

Author(s):

C S Chim ◽

R Pang ◽

R Liang

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

B Lymphocytes ◽

Peripheral Blood ◽

Lymphocytic Leukaemia ◽

Methylation Status ◽

Wnt Signalling ◽

Constitutive Activation ◽

Specific Pcr ◽

Wnt Inhibitor ◽

Inhibitor Genes

Background:Wnt signalling has recently been implicated in the pathogenesis of cancer.Methods:This study investigated the activity of Wnt signalling in peripheral blood chronic lymphocytic leukaemia (CLL) lymphocytes, and the methylation status of seven soluble Wnt antagonist genes, including WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5, by using methylation-specific PCR in the peripheral blood CLL lymphocytes and bone marrow samples of patients with CLL at diagnosis.Results:In the peripheral blood CLL lymphocytes, constitutive activation of Wnt signalling was detected, associated with hypermethylation of the soluble Wnt inhibitor genes. In the diagnostic CLL marrow samples, methylation of the seven genes was detected in up to 36.4% of samples. Moreover, 23 (52.3%) patients had methylation of at least one of the seven genes, of whom 14 (60.8%) had methylation of two or more Wnt inhibitor genes. Apart from an association of advanced age with DKK3 methylation, there was no association of gene hypermethylation with either clinical characteristics (including age, gender, lymphocyte count at diagnosis, Rai stage and poor-risk karyotype) or survival.Conclusion:Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647777 ◽

1973 ◽

Vol 29 (02) ◽

pp. 353-362

Author(s):

J Lisiewicz ◽

A Pituch ◽

J. A Litwin

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

Intravenous Injection ◽

Peripheral Blood ◽

Lymphocytic Leukaemia ◽

Acute Myeloblastic Leukaemia ◽

Demarcation Line ◽

E Coli ◽

Leukaemic Cells ◽

Shwartzman Phenomenon

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.

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Chromosome abnormalities of leukaemic B lymphocytes in chronic lymphocytic leukaemia

Nature ◽

10.1038/283076a0 ◽

1980 ◽

Vol 283 (5742) ◽

pp. 76-78 ◽

Cited By ~ 49

Author(s):

John N. Hurley ◽

Shu Man Fu ◽

Henry G. Kunkel ◽

R. S. K. Chaganti ◽

James German

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

B Lymphocytes ◽

Lymphocytic Leukaemia ◽

Chromosome Abnormalities

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Spontaneous and Oxalate-Induced Radial Segmentation of the Nuclei of Lymphocytes from Peripheral Blood from Patients with Chronic Lymphocytic Leukaemia

Scandinavian Journal of Haematology ◽

10.1111/j.1600-0609.1976.tb02840.x ◽

2009 ◽

Vol 17 (1) ◽

pp. 53-56

Author(s):

Klas Valmin

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

Peripheral Blood ◽

Lymphocytic Leukaemia ◽

Nuclei Of Lymphocytes

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Chronic lymphocytic leukaemia

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0526 ◽

2020 ◽

pp. 5302-5310

Author(s):

Clive S. Zent ◽

Aaron Polliack

Keyword(s):

Bone Marrow ◽

Chronic Lymphocytic Leukaemia ◽

B Cell ◽

Peripheral Blood ◽

B Lymphocyte ◽

Lymphocytic Leukaemia ◽

Bone Marrow Failure ◽

Curative Therapy ◽

Symptomatic Disease ◽

Autoimmune Cytopenias

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.

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