CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells
CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells
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DOI：
10.1182/blood-2003-03-0989
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发表时间：
2003-09-15
期刊：
影响因子：
20.3
通讯作者：
Malavasi, F
中科院分区：
文献类型：
--
作者：
Deaglio, S;Capobianco, A;Malavasi, F
B细胞慢性淋巴细胞白血病（B-CLL）患者的预后通常对表达CD 38的患者不利。我们的工作假设是CD 38不仅是B-CLL的标志物，而且它还发挥着受体的作用，具有决定恶性克隆增殖的致病潜力。在检查的患者中，CD 38水平通常较低，单克隆抗体（mAb）连接在信号传导方面效率低下。其他细胞模型表明，分子密度和表面组织是CD 38功能的关键。白细胞介素2（IL-2）诱导了显着上调和表面重排的CD 38在所有研究的患者。在达到特定表达阈值时，CD 38成为纯化的B-CILL细胞中的有效受体。事实上，mAb连接之后是Ca 2+通量和显著增加的增殖。通过与B细胞受体（BCR）复合物和CD 19的密切相互作用，消除了CD 38作为受体的不适合性。在mAb结合时，CD 38易位至膜脂质微区，如与G（M1）神经节苷脂和CD 81（筏驻留蛋白）共定位所示。最后，IL-2处理的B-CLL细胞中的CD 38信号转导延长了存活时间并诱导了浆母细胞的出现，为Richter综合征的发生提供了发病机制假说。(C)2003年，美国血液学会。
The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CILL cells. Indeed, mAb ligation is followed by Ca2+ fluxes and by a markedly increased proliferation. The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell-receptor (BCR) complex and CD19. On mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a colocalization with the G(M1) ganglioside and with CD81, a raft-resident protein. Finally, CD38 signaling in IL-2-treated B-CLL cells prolonged survival and induced the appearance of plasmablasts, providing a pathogenetic hypothesis for the occurrence of Richter syndrome. (C) 2003 by The American Society of Hematology.