Multiple Myeloma Case Study

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Identifying the therapeutic potential of targeting CD229 in multiple myeloma
Multiple Myeloma (MM) is a disease characterized by the accumulation of plasma cells in patient bone marrows. Although current therapies target the bulk of the tumour, they are ineffective in eradicating the residual chemotherapy-resistant precursor myeloma propagating cells (pre-MCs) that eventually lead to relapse. Thus, identification of markers for targeted therapy of MM precursors is crucial. Screening of myeloma patient samples and cell lines revealed CD229 as a possible diagnostic marker and a therapeutic target in MM as it is more highly expressed and activated in the bulk myeloma cells (CD19-CD38+CD138+) and their precursors (CD19-CD38+CD138-) than other lymphocytes. …show more content…
Anti-tumour activity (colony formation and susceptibility to bortezomib) of CD229 depletion in the bulk MM cells (CD19-CD38+CD138+) and residual “stem-like” precursors (CD19-CD38+CD138-) will be validated. Subsequently, CD229 knockout (KO) and wildtype (WT) MCs and pre-MCs will be profiled for differential protein expression and activation of the molecules in major oncogenic pathways via phosphoproteomics and microarray. To confirm the mechanism, single and double knockdowns of CD229 and identified protein will be tested for anti-tumour activity and treated with pathway-specific chemical …show more content…
To examine the advantage of CD229 depletion in conjunction with current treatment, tumour burden and precursor MC persistence will be monitored via in vivo imaging (IVI) and flow cytometry after bortezomib treatment. To study whether CD229 depletion also affects the ability of precursor cells to re-establish tumours, CD229 KO and WT precursor MCs remaining after partial bortezomib treatment will be transferred into donor NGS mice and latency in tumour growth and load

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