The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

Gordiienko, I M; Shlapatska, Larysa M; Kholodniuk, Valeriia; Sklyarenko, L M; Gluzman, D F; Clark, Edward A.; Sidorenko, Svetlana P.

doi:10.1371/journal.pone.0185940

Cited by 17 publications

(49 citation statements)

References 48 publications

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“…Analysis of primary CLL B cells revealed differences in phenotype profile of CD150 + and CD150 − B cells. CD150 + CLL B cells demonstrate elevated expression levels of cell surface markers CD95, CD180, CD20, CD22, CD62L, chemokine receptor CXCR3 and its ligand CXCL10 in comparison to CD150 − CLL B cells [30,39]. In contrast, CD150 − CLL B cells are characterized by upregulated markers that are associated with aggressive CLL outcome: CD38, CD49d, CD44, CXCR4 and CXCL12 (Fig.…”

Section: Cd150 Is a Candidate For Therapeutic Intervention In Leukemimentioning

confidence: 97%

“…In CLL B cells expressed sCD150 mRNA on significantly higher level than normal peripheral blood CD19 + /CD19 + CD5 + B cells. CD150 was detected in culture supernatant of CLL B cells independently of cell surface CD150 expression and in blood serum of CLL patients and healthy donors [39]. Recombinant sCD150 induce B cells proliferation only at high concentration around 20 μg/ml that is far from physiological [36].…”

Section: Molecular Framework Of Cd150mentioning

confidence: 98%

“…Transcription from Cyt-new exon leads to shift in reading frame and formation of nCD150 isoform with 94 aa cytoplasmic tail lacking classical ITSMs or any another known signaling motifs [33].Besides tumors of CNS nCD150 expression at mRNA level was detected in subpopulation of human tonsillar B cells, normal T cells (CD3 + ), primary DCs, macrophages from peripheral blood, B-lymphoblastoid cell lines, Burkitt's lymphoma cell lines, pre-B acute lymphoblastic leukemia cell lines, HL cell lines, cells of human acute monocytic leukemia cell line THP-1 and MM, primary cases of CLL. It should be noted that nCD150 isoform is predominant in CNS tumors in contrast to normal and malignant B cells where mCD150 is prevailed [31,33,39].…”

Section: Molecular Framework Of Cd150mentioning

confidence: 99%

“…The binding avidity may increase due to the redistribution or clustering after cell activation mediated by other receptor-ligand interactions [40,43]. CD150 is localised to ceramide enriched lipid rafts in T cells, DCs and malignant CLL B cells [13,39,44].…”

Section: Cd150 Signaling Properties and Functions In Hematopoietic Cellsmentioning

confidence: 99%

“…In addition, it coprecipitates with receptor tyrosine phosphatase CD45 and Srk-family kinases Lyn and Fgr, moreover, Lyn uses ITSMs in CD150 cytoplasmic tail as substrates [27,66]. These molecules may connect CD150 with Akt-mTOR axis and also SAP-independent MAPK pathways (ERK1/2, p38 MAPK and JNK1/2) in normal B lymphocytes and in malignant cells of B cell origin [16,27,39,66,69]. In the model of DT40 chicken knockout cell sublines transfected with SAP and/or CD150, CD150mediated Akt phosphorylation requires Syk and SAP, is negatively regulated by Lyn and Btk, but is SHIP independent.…”

Section: Cd150 Signaling Properties and Functions In Hematopoietic Cellsmentioning

confidence: 99%

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SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Gordiienko

Shlapatska

Kovalevska

et al. 2019

Clinical Immunology

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SLAMF1/CD150 receptor is a founder of signaling lymphocyte activation molecule (SLAM) family of cell-surface receptors. It is widely expressed on cells within hematopoietic system. In hematologic malignancies CD150 cell surface expression is restricted to cutaneous T-cell lymphomas, few types of B-cell non-Hodgkin's lymphoma, near half of cases of chronic lymphocytic leukemia, Hodgkin's lymphoma, and multiple myeloma. Differential expression among various types of hematological malignancies allows considering CD150 as diagnostical and potential prognostic marker. Moreover, CD150 may be a target for antibody-based or measles virus oncolytic therapy. Due to CD150 signaling properties it is involved in regulation of malignant cell fate decision and tumor microenvironment in Hodgkin's lymphoma and chronic lymphocytic leukemia. This review summarizes evidence for the important role of CD150 in pathogenesis of hematologic malignancies.

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Section: Cd150 Is a Candidate For Therapeutic Intervention In Leukemimentioning

confidence: 97%

Section: Molecular Framework Of Cd150mentioning

confidence: 98%

Section: Molecular Framework Of Cd150mentioning

confidence: 99%

Section: Cd150 Signaling Properties and Functions In Hematopoietic Cellsmentioning

confidence: 99%

Section: Cd150 Signaling Properties and Functions In Hematopoietic Cellsmentioning

confidence: 99%

See 3 more Smart Citations

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Gordiienko

Shlapatska

Kovalevska

et al. 2019

Clinical Immunology

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CD markers variations in chronic lymphocytic leukemia: New insights into prognosis

Vosoughi

Bagheri

Hosseinzadeh

et al. 2019

Journal Cellular Physiology

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Chronic lymphocytic leukemia (CLL) is one of the most commonly occurring adult leukemias that is associated with clonal accumulation of mature apoptosis-resistant B-cells in bone marrow, peripheral blood, and specific tissues. Different pathogenesis factors can contribute to the aggression of the clinical course in this disease.Cytogenetic abnormalities and surface biomarkers of neoplastic CLL cells can be effective in the outcome of CLL, and the examination of changing CD markers expressions in the progression of CLL can be related to the prognosis of this disease. Changing expression levels of CD markers on lymphocytes and other cells in CLLpatients can play a role in the aggressive clinical outcomes such as organomegaly, immunodeficiency, and advanced disease stages through their interaction with CLL microenvironment. Given the involvement of CD markers in the pathogenesis of CLL, it can be stated that recognizing the expression changes of CD markers in the cells involved in CLL can be a proper approach to evaluate prognosis among these patients.

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SLAMF6 in health and disease: Implications for therapeutic targeting

Yigit

Wang

Herzog

et al. 2019

Clinical Immunology

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Effective immune responses develop after a well-orchestrated series of events that include recognition, immune cell interactions and activation/inhibition of signaling pathways. The signaling lymphocyte activation molecule family (SLAMF) of cell surface receptors, which consists of nine transmembrane proteins (SLAMF1-9) expressed at different levels, are involved in viral and bacterial recognition, serve as co-stimulatory molecules at immune synapses, and modulate myeloid and lymphocyte development. SLAMF receptors are homophilic receptors, with the exception of SLAMF2 and SLAMF4, and are only expressed on hematopoietic cells. Their adaptors, SLAM associated protein (SAP) and Ewing's sarcoma-associated transcript 2 (EAT-2), bind to the cytoplasmic tails and control the functions and magnitude of SLAMF receptor signaling. In this review, we focus on the current knowledge on the role of SLAMF6 receptor in regulating immune functions and recent findings describing how SLAMF6 can be exploited as a target in human malignancies. The SLAM family of immune cell surface receptors is a member of the CD2 subfamily of the immunoglobulin (Ig) superfamily consisting of nine members, SLAMF1-9 [1-4]. SLAMF receptors are type I transmembrane glycoproteins comprised of an extracellular membrane containing an N-terminal V-Ig domain followed by a C2-Ig domain in the extracellular region (this set is duplicated in SLAMF3), a transmembrane region, and an intracellular cytoplasmic tail containing tyrosine based switch motifs (ITSM). Notable exceptions to this structure include SLAMF2, which has a glycosyl-phosphatidyl-inositol (GPI) membrane anchor and like SLAMF8 and SLAMF9 lack ITSM motifs [5-8]. Binding of SLAM associated adaptors; SAP and EAT-2, to cytoplasmic tails of various SLAMFs regulate their function on different immune cells. Expression of SLAMFs and their adaptors is restricted to hematopoietic cells. In addition, the gene loci are located on chromosome 1 in both mice and humans, except SAP, which is located on the X chromosome [9](Figure 1). All SLAMFs are homophilic receptors aside from SLAMF2 and SLAMF4, which bind each other [10-12]. The determination of the SLAMF3, SLAMF5 and SLAMF6 crystal structures revealed in-trans interactions through their IgV domains (SLAMF3 unpublished data, generously donated by Profs. Steve Almo and Stanley Nathenson, Albert Einstein College of Medicine (Figure 2) [13, 14]. Engagement of SLAMF ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T receptors on immune cells (e.g. APC -T cell) trigger inhibitory or activating signals that modulate cellular responses. Within these homophilic and heterophilic interactions, the binding affinities for each SLAMF varies (SLAMF3 nM, SLAMF5 sub-M, SLAMF6 ~ 2M, SLAMF2/4 ~4M, SLAMF1 ~200 M) which likely contributes to functional differences within the family of receptors [12-15]. In addition to being self-ligands, SLAMF1 also serves as an entry receptor for Measles virus [16, 17] while SLAMF1, SLAMF2 and SLAMF6 have been demonstrated to interact...

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The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

Cited by 17 publications

References 48 publications

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

CD markers variations in chronic lymphocytic leukemia: New insights into prognosis

SLAMF6 in health and disease: Implications for therapeutic targeting

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