Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70

Lafarge, Sandrine; Hou, Sen; Pauls, Samantha D.; Johnston, James B.; Gibson, Spencer B.; Marshall, Aaron J.

doi:10.1016/j.leukres.2015.04.016

Cited by 13 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using phosphorylated (p-)p38, a mitogen-activated protein (MAP) kinase, we defined ''active'' and ''inactive'' cells and analyzed the expression of selected markers in these subpopulations (Figure S6A). This analysis confirmed that p-p38-positive cells also displayed higher levels of p-p65 and p-STAT1 and revealed higher levels of CD27 expression in these ''active'' cells, which may indicate engagement of the B cell receptor (Lafarge et al, 2015). Interestingly, staining for cleaved PARP and cleaved CASPASE3 was enhanced more strongly in ''inactive'' cells upon treatment (Figures S6B and S6C).…”

Section: Cll B Cells With Samhd1 Mutations Are Highlysupporting

confidence: 69%

“…Our CyTOF analysis revealed that CLL B cells, identified by CD19 and CD5 staining, contained two subpopulations of cells, distinguishable by expression of CD27 and phosphorylation of p65, p38, and STAT1. Activation of NF-kB, MAP kinase, and STAT signaling pathways has been reported in CLL (Frank et al, 1997;Herishanu et al, 2011;Ringshausen et al, 2004;Shukla et al, 2018), and CD27 is upregulated in response to B cell receptor engagement (Lafarge et al, 2015). We therefore labeled these cell populations ''active'' and ''inactive.''…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Cll B Cells With Samhd1 Mutations Are Highlysupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Using phosphorylated (p-) p38, a MAP kinase, we defined “active” and “inactive” cells and analysed the expression of selected markers in these subpopulations (Supplementary Figure 5A). This analysis confirmed that p-p38 positive cells also displayed higher levels of p-p65 and p-STAT1 and revealed higher levels of CD27 expression in these “active” cells, which may indicate engagement of the B cell receptor (Lafarge et al, 2015). Interestingly, staining for cleaved PARP and cleaved CASPASE3 was enhanced more strongly in “inactive” cells upon treatment (Supplementary Figure 5B,C).…”

Section: Resultssupporting

confidence: 68%

“…Our CyTOF analysis revealed that CLL B cells identified by CD19 and CD5 staining contained two sub-populations of cells, distinguishable by expression of CD27 and phosphorylation of p65, p38 and STAT1. Activation of NFκB, MAP kinase and STAT signalling pathways has been reported in CLL (Frank et al, 1997; Herishanu et al, 2011; Ringshausen et al, 2004; Shukla et al, 2018) and CD27 is upregulated in response to B cell receptor engagement (Lafarge et al, 2015). We therefore labelled these cell populations “active” and “inactive”.…”

Section: Discussionmentioning

confidence: 99%

SAMHD1 limits the efficacy of forodesine in leukaemia by protecting cells against cytotoxicity of dGTP

Davenne

Klintman

Sharma

et al. 2020

Preprint

View full text Add to dashboard Cite

Immucillin H, chronic lymphocytic leukaemia 28 29 Running title 30 SAMHD1 protects against dGTP toxicity 31 -2 -Graphical Abstract 32 33 34 Highlights 35 • SAMHD1-deficient cells die upon exposure to deoxyribonucleosides (dNs) 36 • Deoxyguanosine (dG) is the most toxic dN, inducing apoptosis in cells lacking 37 SAMHD1 38 • SAMHD1-mutated leukaemic cells can be killed by dG and the PNP-inhibitor 39 forodesine 40 41 In Brief 42 SAMHD1 degrades deoxyribonucleoside triphosphates (dNTPs), the building blocks 43 of DNA. Davenne et al. found that SAMHD1 protects cells against dNTP imbalances. 44Exposure of SAMHD1-deficient cells to deoxyguanosine (dG) results in increased 45 intracellular dGTP levels and subsequent apoptosis. This can be exploited to 46 selectively kill cancer cells that acquired SAMHD1 mutations. 47 -3 - Summary 48The anti-leukaemia agent forodesine causes cytotoxic overload of intracellular 49 deoxyguanosine triphosphate (dGTP) but is efficacious only in a subset of patients. 50We report that SAMHD1, a phosphohydrolase degrading deoxyribonucleoside 51 triphosphates (dNTPs), protected cells against the effects of dNTP imbalances. 52 SAMHD1-deficient cells induced intrinsic apoptosis upon provision of 53deoxyribonucleosides, particularly deoxyguanosine (dG). Moreover, dG and 54 forodesine acted synergistically to kill cells lacking SAMHD1. Using mass cytometry, 55we found that these compounds killed SAMHD1-deficient malignant cells from patients 56 with chronic lymphocytic leukaemia (CLL). Normal cells and CLL cells from patients 57 without SAMHD1 mutation were unaffected. We therefore propose to use forodesine 58 as a precision medicine for leukaemia, stratifying patients by SAMHD1 genotype or 59 expression. 60

show abstract

“…ZAP-70 is usually present on the surface of T and NK cells, but not on normal B cells. However, CLL cells also possess this marker, and it appears that CD 38 binds with CD31 ligand, expressed by NLCs and leads to ZAP-70 phosphorylation, which will further activate the BCR and through signaling pathways like PI3Ks and BTK will enhance CLL cells proliferation and survival [141].…”

Section: Enhancing Survival and Antiapoptotic Effectmentioning

confidence: 99%

Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells

Mesaros,

Jimbu,

Neaga

et al. 2020

Biomedicines

View full text Add to dashboard Cite

Macrophages are terminally differentiated innate immune cells. Through their activation, they can be polarized towards the pro-inflammatory M1 type or the wound healing-associated, anti-inflammatory M2 type macrophages. In the tumor microenvironment (TME), M2 is the dominant phenotype and these cells are referred to as tumor-associated macrophages (TAMs). TAMs secrete cytokines and chemokines, exerting an antiapoptotic, proliferative and pro-metastatic effect on the tumor cells. TAMs can be found in many cancers, including chronic lymphocytic leukemia (CLL), where they are called nurse-like cells (NLCs). Despite the generally indolent behavior of CLL, the proportion of treatment-refractory patients is significant. As with the majority of cancers, despite significant recent progress, CLL pathogenesis is poorly understood. The emerging role of the TME in nurturing the neoplastic process warrants the investigation of macrophages as a significant pathogenetic element of tumors. In this paper, we review the current knowledge on the role of stromal macrophages in CLL.

show abstract

Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70

Cited by 13 publications

References 37 publications

SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP

SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP

SAMHD1 limits the efficacy of forodesine in leukaemia by protecting cells against cytotoxicity of dGTP

Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells

Contact Info

Product

Resources

About