The role of surface molecule CD229 in Multiple Myeloma

Olson, Michael; Radhakrishnan, Sabarinath Venniyil; Luetkens, Tim; Atanackovic, Djordje

doi:10.1016/j.clim.2018.10.006

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…In this study, we found that both CD229 and CD319 were widely expressed on MM cells. This finding was in agreement with Olson et al (25) , who verified that CD229 has a wide, strong, and homogenous expression on malignant PCs. These results are also supported by Ishibashi et al (7) and Sriram et al (26) who reported that CD319 was highly expressed cells of MM and correlated with progression of the disease.…”

Section: Discussionsupporting

confidence: 93%

“…In this work, as we found that patients with low expression of CD319 and CD229 and c-Maf negative have a better response to treatment, we suggest the predictive significance of these markers. This is supported by Olson et al (25) who demonstrated the poor prognostic value of CD229 in MM and Radhakrishnan et al (27) who stated that CD229 is a poor prognostic marker in MM and its target therapy may eradicate terminally differentiated MM cells and clonotypic MMpropagating cells. Radhakrishnan et al (27) also stated that targeting CD229 can treat the MM-resistant cases and potentially providing long-lasting responses and Postelnek et al (28) , who demonstrated the prognostic role of CD319, reported that a high concentration of CD319 in the microenvironment of BM may suppress elotuzumab effects in MM patients.…”

Section: Discussionmentioning

confidence: 75%

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Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

Ebian¹,

Wahab²,

Elbasateeny³

et al. 2021

The Egyptian Journal of Hospital Medicine

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Background: Ly-9 (CD229) and SLAMF7 (CD319) are more stable markers that could be used to replace the less stable conventional markers CD138 and CD38 in multiple myeloma (MM) patient follow-up. In those patients, the correlation between these markers and the histopathologic marker c-Maf has not been well investigated. Objective: To assess the predictive value of CD229, CD319, and c-MAF overexpression on outcome of treatment in MM patients. Patients and Methods: 61 newly diagnosed multiple myeloma patients were involved in this prospective study. Flow cytometric analysis of bone marrow (BM) samples for CD229 PE, CD319 PE, CD138 PerCP and CD38FITC as well as BM biopsy immunohistochemically were analyzed for c-Maf expression Results: CD229 and CD319 were highly expressed in (≥93.95%) and (≥95.6%) of MM patients respectively. c-Maf was positive in (29.5%) of patients. In MM patients with high expression of CD229 and CD319 as well as those with c-Maf positivity showed high serum Ca ++ , β2M, CD138 and CD38. CD229 was significantly correlated with CD319, CD38, CD138, β2M and serum Ca (p-values were< 0.001,0.01, 0.01, 0.009, and 0.02 respectively). Patients with overexpression of CD 229, CD319 and c-Maf were more refractory to treatment (p-values were <0.001,<0.001 and <0.001 respectively). Conclusion:We detected that both CD229 and CD319 were significantly overexpressed on MM cells and correlated significantly with CD138 and CD38, suggesting their use as alternative markers for MM diagnosis as well as followup. Patients with CD229,CD319, and c-Maf overexpression were associated with a significant poor response to therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 75%

Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

Ebian¹,

Wahab²,

Elbasateeny³

et al. 2021

The Egyptian Journal of Hospital Medicine

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“…This has been already reported by others studying myeloma cells in bone marrow [17][18][19]. Moreover, it has been suggested that CD229 could have a relevant biological role in the survival of myeloma cells [25], and that its expression is higher in myeloma-propagating cells, which are more quiescent, and more drug-resistant than the common malignant plasma cell [26].…”

Section: Discussionsupporting

confidence: 56%

CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma

Roncador

Puñet-Ortiz

Maestre

et al. 2022

Cancers

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CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC). In this study, we used a new mAb against the cytoplasmic region of CD229 to study the expression of CD229 on normal tissues and B-cell malignancies, including multiple myeloma (MM), using tissue microarrays. We showed CD229 to be restricted to hematopoietic cells. It was strongly expressed in all cases of MM and in most marginal-zone lymphomas (MZL). Moderate CD229 expression was also found in chronic lymphocyte leukemia (CLL), follicular (FL), classic mantle-cell (MCL) and diffuse large B-cell lymphoma. Given the high expression on myeloma cells, we also analyzed for the presence of soluble CD229 in the sera of these patients. Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target.

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“…SLAMF3, also known as Ly9 or CD229, is another receptor of the SLAM family. It has a homogeneous expression on MM cells, which is stable regardless of the disease stage and exposure to different treatments, and it plays an essential role in the survival of MM cells (103–106). Moreover, CD19 − CD138 − MM cells, which represent a quiescent, drug-resistant myeloma-propagating cell population (107), are highly positive for CD229 (104).…”

Section: Preclinical Studiesmentioning

confidence: 99%

Chimeric Antigen Receptor-Modified T Cell Therapy in Multiple Myeloma: Beyond B Cell Maturation Antigen

et al. 2019

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Chimeric antigen receptor (CAR)-modified T cell therapy is a rapidly emerging immunotherapeutic approach that is revolutionizing cancer treatment. The impressive clinical results obtained with CAR-T cell therapy in patients with acute lymphoblastic leukemia and lymphoma have fueled the development of CAR-T cells targeting other malignancies, including multiple myeloma (MM). The field of CAR-T cell therapy for MM is still in its infancy, but remains promising. To date, most studies have been performed with B cell maturation antigen (BCMA)-targeted CARs, for which high response rates have been obtained in early-phase clinical trials. However, responses are usually temporary, and relapses have frequently been observed. One of the major reasons for relapse is the loss or downregulation of BCMA expression following CAR-T therapy. This has fostered a search for alternative target antigens that are expressed on the MM cell surface. In this review, we provide an overview of myeloma target antigens other than BCMA that are currently being evaluated in pre-clinical and clinical studies.

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The role of surface molecule CD229 in Multiple Myeloma

Cited by 12 publications

References 32 publications

Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma

Chimeric Antigen Receptor-Modified T Cell Therapy in Multiple Myeloma: Beyond B Cell Maturation Antigen

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