Natural Phosphorylation of CD5 in Chronic Lymphocytic Leukemia B Cells and Analysis of CD5-Regulated Genes in a B Cell Line Suggest a Role for CD5 in Malignant Phenotype

Gary-Gouy, Hélène; Sainz-Perez, Alexander; Marteau, Jean‐Brice; Marfaing-Koka, Anne; Delić, Jozo; Merle‐Béral, Hélène; Galanaud, Pierre; Dalloul, Ali

doi:10.4049/jimmunol.179.7.4335

Cited by 52 publications

(53 citation statements)

References 68 publications

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“…There is also evidence to suggest that CD5 is involved in promoting survival. Natural phosphorylation of regulatory tyrosines on CD5 in CLL B cells reflects chronic activation (18), and sustained signaling through the BCR promotes further expression of CD5 (37). Thus, BCR engagement favors the expression of CD5 (38) which provides viability signals for B cells in a subset of CLL patients (39,40).…”

Section: Discussionmentioning

confidence: 99%

“…These cells contain transcripts for CD5-E1B but not for CD5-E1A (6,16). Daudi B cells, which are negative for surface CD5 but transfected with cd5-E1A to induce membrane CD5 expression of CD5, were supplied by Prof. A. Dalloul (University of Nancy, Nancy, France) (17,18). Jurkat T cells and COS-1 cells were purchased from the American Type Culture Collection.…”

Section: Cell Preparationmentioning

confidence: 99%

See 1 more Smart Citation

Selection of the Alternative Exon 1 from thecd5Gene Down-Regulates Membrane Level of the Protein in B Lymphocytes

Garaud¹,

Dantec²,

Berthou³

et al. 2008

The Journal of Immunology

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The human cd5 gene has two alternative exons 1: exon 1A (E1A) which encodes the full-length (FL) CD5 protein and exon 1B (E1B) which encodes a truncated (TR) isoform. The FL variant of CD5 protein is translocated to the plasma membrane, while its TR variant is retained in the cytoplasm. Because there is an inverse relationship between the levels of FL-CD5 and TR-CD5 in B cells, we have addressed the issue of how the selection of exon 1 is determined. In leukemic B cells, DNA methyltransferase (DNMT)1-induced methylation of E1B prevents its transcription. Furthermore, the level of mRNA for DNMT1 correlates inversely with that of mRNA for CD5-E1B. However, suppression of E1B transcription is incomplete, and some molecules of TR-CD5 continue to be synthesized. Bortezomid-induced inhibition of the proteasome establishes that these TR-CD5 molecules are cleared through the ubiquitin-proteasome pathway. Transfection of CD5 mutants into COS-1 cells locates the ubiquitin-binding site at the second destruction box of the extracellular region of CD5. Activation of the B cells by anti-IgM, Staphylococcus aureus Cowan I (SAC), or PMA up-regulates DNMT1, and thereby CD5-E1A mRNA at the expense of CD5-E1B mRNA. Aberrant synthesis of TR-CD5 is thus offset by balanced degradation of excessive protein. Dysregulation of these mechanisms reduces the expression level of membrane CD5, and thereby diminishes the threshold of the response by cells expressing CD5.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Preparationmentioning

confidence: 99%

Selection of the Alternative Exon 1 from thecd5Gene Down-Regulates Membrane Level of the Protein in B Lymphocytes

Garaud¹,

Dantec²,

Berthou³

et al. 2008

The Journal of Immunology

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“…Another interesting observation was reported by Richardson et al [36] who identified an enhanced expression of CCR7 on ZAP70(+) B-CLL cells, leading to an increased responsiveness of CCR7 to its ligands CCL19 and CCL21. Gary-Gouy et al [61] found that CD5 phosphorylation may lead to an additional expression increase of CCR7 on B-CLL cells. Furthermore, Ticcioni et al [56] found that CCL19 and CCL21 contribute to prolonged survival of B-CLL cells by activating ERK1/2 and Akt.…”

Section: Ccl19 Ccl21 and Their Common Receptor Ccr7mentioning

confidence: 99%

“…Although it is predominantly expressed on naïve T lymphocytes, CCR7 is also detectable on B lymphocytes (on which it was initially identified) [1,58,59]. CCR7 also has been demonstrated to have a great impact on the development of secondary lymphoid organs [60,61]. Till et al [60] demonstrated that due to increased CCR7 expression on B-CLL cells and CCL19 and CCL21 expression in high endothelial venules, TEM was significantly higher for malignant B cells of patients with LN involvement compared to those without this organomegaly.…”

Section: Ccl19 Ccl21 and Their Common Receptor Ccr7mentioning

confidence: 99%

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

2009

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International audienceChemokines are centrally involved in leukocyte migration, homing and haematopoiesis. Besides these physiological aspects, their role in pathological processes especially with respect to solid tumour and haematological neoplasias is well established. In this context, the focus was set here on disclosing their contribution in B cell chronic lymphocytic leukaemia (B-CLL), which is regarded as the most characteristic low-grade lymphoma. Up to now, it has been demonstrated that several chemokines are involved in migration of B-CLL cells to lymph nodes, secondary lymphoid organs and bone marrow. Moreover, some chemokines are known to have an anti-apoptotic effect and thus contribute to the survival of B-CLL cells. By interfering with both of these aspects, new therapeutic targets for this yet incurable disease may be developed. Furthermore, a correlation can be drawn between the concentration of some chemokines in patients' serum, the expression of their respective receptors on B-CLL cells and well-established predictive clinical parameters. Consequently, further systematic investigation of the chemokine network may lead to the identification of new diagnostic and prognostic markers. This review focuses on the impact of chemokines and their receptors on B-CLL pathophysiology and points out potential implications for both treatment and diagnosis

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“…It is known that malignant cells from CLL are undergoing a process of continuous stimulation due to CD5 activation and cell survival. (Gary-Gouy et al, 2007) A continuous activation of an antiapoptotic pathway explains the CLL cells survival. Apolipoprotein E4-very low density lipoproteins is responsible for the high level of apoptosis in CLL cells.…”

Section: Cholesterol Metabolism Disordermentioning

confidence: 99%

Cholesterol and Triglycerides Metabolism Disorder in Malignant Hemopathies

Mihăilă¹

2012

Dyslipidemia - From Prevention to Treatment

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Natural Phosphorylation of CD5 in Chronic Lymphocytic Leukemia B Cells and Analysis of CD5-Regulated Genes in a B Cell Line Suggest a Role for CD5 in Malignant Phenotype

Abstract: Material

Cited by 52 publications

References 68 publications

Selection of the Alternative Exon 1 from thecd5Gene Down-Regulates Membrane Level of the Protein in B Lymphocytes

Selection of the Alternative Exon 1 from thecd5Gene Down-Regulates Membrane Level of the Protein in B Lymphocytes

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

Cholesterol and Triglycerides Metabolism Disorder in Malignant Hemopathies

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