2012年9月14日 訊 /生物谷BIOON/ --Moffitt癌癥中心研究人員發(fā)現(xiàn),，記憶調(diào)節(jié)性T細(xì)胞物理特性的變化可以預(yù)測骨髓增生異常綜合征（MDS）發(fā)展成急性髓細(xì)胞性白血病的風(fēng)險，這一發(fā)現(xiàn)可能改善MDS患者的預(yù)測,，同時也有助于開發(fā)更好的治療手段。
這項研究發(fā)表在Journal of Immunology雜志上,。骨髓增生異常綜合征是起源于造血干細(xì)胞的一組異質(zhì)性髓系克隆性疾病,，特點是髓系細(xì)胞分化及發(fā)育異常，表現(xiàn)為無效造血,、難治性血細(xì)胞減少,、造血功能衰竭，高風(fēng)險向急性髓系白血?。ˋML）轉(zhuǎn)化,。
三分之一的MDS患者會出現(xiàn)骨髓造血功能衰竭，并在確診后的最初幾年內(nèi)演變成急性髓系白血病,。MDS患者骨髓中產(chǎn)生的血細(xì)胞是無效的,，這常常使得患者貧血，需要頻繁輸血,。
這種疾病可能是由于癌癥化療治療或放療導(dǎo)致的結(jié)果,，或者與骨髓故障導(dǎo)致的頻繁輸血以及隨后的鐵超負(fù)荷造成的。反復(fù)輸血往往會造成鐵的積累,，而患者身體中用來減少鐵積累的機(jī)制缺乏,，病人的器官往往鐵超負(fù)荷，導(dǎo)致心臟衰竭,、肝損傷,，出現(xiàn)對感染的易感性和其他并發(fā)癥。骨髓移植可能是MDS患者往往必須采取的治療策略,。為了了解更多關(guān)于MDS疾病的發(fā)展,，Moffitt的研究人員重點研究免疫系統(tǒng)，特別是被稱為調(diào)節(jié)性T細(xì)胞在骨髓增生異常綜合征中的作用,。
研究人員說,，調(diào)節(jié)性T細(xì)胞在實體瘤的腫瘤免疫入侵中發(fā)揮重要作用，但很少有人知道調(diào)節(jié)性T細(xì)胞在癌前病變中所發(fā)揮的作用,。免疫學(xué)系Pearlie K. Epling藥學(xué)博士說： 我們重點研究了被稱為記憶調(diào)節(jié)性T細(xì)胞的調(diào)節(jié)性T細(xì)胞亞群,。
研究發(fā)現(xiàn)，MDS患者記憶調(diào)節(jié)性T細(xì)胞發(fā)生了物理特性的變化或表型的變化,，這提示它們可能會以與效應(yīng)記憶性Ť細(xì)胞激活相似的方式激活,。通過觀察病人的效應(yīng)記憶調(diào)節(jié)性T細(xì)胞,，我們能夠確定MDS患者疾病的進(jìn)展，預(yù)測發(fā)展成急性髓細(xì)胞性白血病的風(fēng)險,。研究人員說,，效應(yīng)記憶調(diào)節(jié)性T細(xì)胞的增加可能反映了免疫抑制效應(yīng)的激活，并可能是預(yù)示患者免疫微環(huán)境轉(zhuǎn)換的最早生物標(biāo)志物,。（生物谷：Bioon.com）
doi:10.4049/jimmunol.1200602
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Expansion of Effector Memory Regulatory T Cells Represents a Novel Prognostic Factor in Lower Risk Myelodysplastic Syndrome
Adam W. Mailloux, Chiharu Sugimori, Rami S. Komrokji, Lili Yang, et al.
Myelodysplastic syndromes are premalignant diseases characterized by cytopenias, myeloid dysplasia, immune dysregulation with association to autoimmunity, and variable risk for acute myeloid leukemia transformation. Studies of FOXP3+ regulatory T cells (Tregs) indicate that the number and/or activation state may influence cancer progression in these patients. Focusing on patients with a lower risk for leukemia transformation, 18 (34.6%) of 52 patients studied displayed an altered Treg compartment compared with age-matched controls. Delineation of unique Treg subsets revealed that an increase in the absolute number of CD4+FOXP3+CD25+CD127lowCD45RA−CD27− Tregs (effector memory Tregs [TregEM]) was significantly associated with anemia (p = 0.046), reduced hemoglobin (p = 0.038), and blast counts ≥5% (p = 0.006). In healthy donors, this TregEM population constitutes only 2% of all Tregs (one to six Tregs per microliter) in peripheral blood but, when isolated, exhibit greater suppressive activity in vitro. With a median follow-up of 3.1 y (range 2.7–4.9 y) from sample acquisition, increased numbers of TregEM cells proved to have independent prognostic importance in survival estimates, suggesting that enumeration of this Treg subset may be a more reliable indicator of immunological escape than FOXP3+ T cells as a whole. Based on multivariate analyses, TregEM impacted survival independently from myeloblast characteristics, cytopenias, karyotype, and comorbidities. Based on these findings, TregEM cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes.
