B細胞淋巴瘤，通常發(fā)生于兒童和成年人,，是一種攻擊免疫系統(tǒng)中B細胞的癌癥類型。近日,，費城兒童醫(yī)院的研究員明確了驅(qū)動癌癥信號的分子通路,。
費城兒童醫(yī)院腫瘤科研究員Andrei Thomas-Tikhonenko博士說,，我們的研究表明如何制定更具體的療法，能選擇性地殺死一類淋巴瘤中的腫瘤細胞,。
相關(guān)研究在動物細胞和人類細胞培養(yǎng)中進行研究,，研究論文發(fā)表在Journal of Clinical Investigation雜志上。
一個基因通常會編碼產(chǎn)生一種蛋白質(zhì),，在細胞的生長或監(jiān)管中發(fā)揮重要積極,。然而，當該基因發(fā)生突變或過量時,，通?？梢詫е掳┌Y發(fā)生。該項研究的重點在于被稱為MYC基因的一個癌基因,，主要研究Myc基因如何推動B細胞淋巴瘤的發(fā)生與發(fā)展,。Myc基因處于較高水平，細胞生長失控,，這是癌癥的一個標志,。
研究人員關(guān)注于細胞表面受體CD19的關(guān)鍵作用，他們發(fā)現(xiàn)CD19對穩(wěn)定Myc蛋白來說是絕對必要的,。 當Myc基因是穩(wěn)定的,，并處于較高水平時，Myc基因會促使癌癥發(fā)展,。Myc蛋白水平高的患者更可能死于淋巴瘤,。
Myc蛋白水平高的患者CD19水平也高，在這項研究中,，研究人員描述了一個前所未知的依賴于CD19的分子通路,。CD19控制Myc基因通路上的開關(guān)。沒有CD19的,，就沒有Myc基因,，他補充說，控制通斷開關(guān)可能代表了治療淋巴瘤的有力工具,。
Thomas-Tikhonenko表示：目前已經(jīng)有腫瘤的臨床試驗測試對抗CD19受體的抗體,。這種抗體能殺死所有的B細胞，從而削弱免疫系統(tǒng),。他的研究表明了解CD19的信號途徑可以使研究人員能夠設(shè)計一個更具體的治療方法,，能選擇性地殺死腫瘤細胞，同時保留健康的B細胞,。
他補充說,，他的實驗室將進一步研究探討這些分子途徑以及如何將研究成果轉(zhuǎn)化為未來抗癌治療手段,。（生物谷：Bioon.com）
doi:10.1172/JCI45851
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CD19 is a major B cell receptor–independent activator of MYC-driven B-lymphomagenesis
Elaine Y. Chung1, James N. Psathas1, Duonan Yu2, Yimei Li3, Mitchell J. Weiss2,4 and Andrei Thomas-Tikhonenko1,4
PAX5, a B cell–specific transcription factor, is overexpressed through chromosomal translocations in a subset of B cell lymphomas. Previously, we had shown that activation of immunoreceptor tyrosine-based activation motif (ITAM) proteins and B cell receptor (BCR) signaling by PAX5 contributes to B-lymphomagenesis. However, the effect of PAX5 on other oncogenic transcription factor-controlled pathways is unknown. Using a MYC-induced murine lymphoma model as well as MYC-transformed human B cell lines, we found that PAX5 controls c-MYC protein stability and steady-state levels. This promoter-independent, posttranslational mechanism of c-MYC regulation was independent of ITAM/BCR activity. Instead it was controlled by another PAX5 target, CD19, through the PI3K-AKT-GSK3β axis. Consequently, MYC levels in B cells from CD19-deficient mice were sharply reduced. Conversely, reexpression of CD19 in murine lymphomas with spontaneous silencing of PAX5 boosted MYC levels, expression of its key target genes, cell proliferation in vitro, and overall tumor growth in vivo. In human B-lymphomas, CD19 mRNA levels were found to correlate with those of MYC-activated genes. They also negatively correlated with the overall survival of patients with lymphoma in the same way that MYC levels do. Thus, CD19 is a major BCR-independent regulator of MYC-driven neoplastic growth in B cell neoplasms.
