NAMPT and LYST as potential therapeutic targets in multiple myeloma

The compound displaying the title of the Institute for Medical Research, Kuala Lumpur, Malaysia
The compound displaying the title of the Institute for Medical Research, Kuala Lumpur, Malaysia

Multiple myeloma (MM) is a type of blood cancer that affects the plasma cell. It is a rare form of cancer, accounting for 1% of all cancer diagnoses and 2% of all cancer deaths. The incidence rates increase with age and they are higher in males than females. The etiology of MM are not well established, several risk factors such as age, gender, and genetic variations are considered to be responsible for the occurrence of this disease.

Previous studies have shown that changes in chromosomes copy number, as well as genetic and epigenetic alterations play an important role in the initiation and progression of MM. Despite many recent advances in the treatment of MM, it still remains incurable. New effective treatment regimens are urgently needed to improve prognosis and survival outcomes in patients with MM.

Our research team had previously found high chromosomal gains where nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) were localised. Therefore, we aimed to evaluate the biological functions of NAMPT and LYST genes on growth and survival of RPMI-8226 myeloma cell line. We knocked down the gene and then determined the cell growth rate and cell death events (apoptosis) in the cell line and compared them against control. Interestingly, we found that NAMPT and LYST play critical functions in controlling myeloma cell growth through suppression of cell growth and activation of myeloma cell death events.

Our findings show that NAMPT and LYST might be potential therapeutic targets in MM. However, these results are preliminary, yet, more research is necessary to confirm and evaluate these findings.

Chinese language summary

多發性骨髓瘤是一種影響漿細胞的血液癌。它是罕見的癌症形式, 佔所有癌症診斷的1%及所有癌症死亡的2%。發病率隨年齡增長而增加,男性高於女性。多發性骨髓瘤的病因尚未明確,據認為,幾種危險因素,如年齡,性別,遺傳變異都是導致這種疾病發生的原因。 以前的研究表明,染色體拷貝數,遺傳和表觀遺傳的變化在多發性骨髓瘤的起始和進展中起重要作用。儘管最近在多發性骨髓瘤的治療方面取得了許多進展,但多發性骨髓瘤仍然無法治愈。迫切需要新的有效治療方案來改善多發性骨髓瘤患者的預後和生存結果。
以前,我們的研究團隊發現,NAMPTLYST所在的染色體拷貝數增益, 發生在許多本國的多發性骨髓瘤患者。因此,我們旨在確定NAMPTLYST基因對RPMI-8226骨髓瘤細胞系生長和存活的生物學功能。我們敲除NAMPTLYST基因,然後測定RPMI-8226骨髓瘤的細胞增殖率和細胞凋亡,並與對照組比較。有趣的是,我們發現NAMPTLYST通過抑制骨髓瘤細胞增殖和激活細胞凋亡,起到控制骨髓瘤細胞生長的關鍵作用。

從我們的研究結果,我們建議NAMPTLYST可能是多發性骨髓瘤的潛在治療靶點。然而,這些結果是初步的,需要更多的研究來確認和評估這些發現。

 

Reference:

Bong IP, Ng CC, Fakiruddin SK, Lim MN, Zakaria Z. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study. Bosn J Basic Med Sci. 2016 Nov 10;16(4):268-275. doi: 10.17305/bjbms.2016.1568. [Epub ahead of print]

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