Bendall Linda J, James Alexander, Zannettino Andrew, Simmons Paul J, Gottlieb David J, Bradstock Kenneth F
Westmead Institute for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia.
Immunol Cell Biol. 2003 Aug;81(4):311-9. doi: 10.1046/j.1440-1711.2003.t01-1-01174.x.
Previous studies have shown that the antibody 7H9D6 identifies CD44, a glycoprotein receptor for hyaluronic acid. 7H9D6 recognizes an epitope of CD44 that is not always present on CD44 molecules. The 7H9D6 antibody bound to the hyaluronic acid binding domain of CD44 and inhibited cell adhesion to immobilized hyaluronic acid. However, the expression of the 7H9D6 epitope was not sufficient for hyaluronic acid binding. Immunofluorescent staining with 7H9D6 revealed a punctate surface staining pattern, suggesting that CD44 molecules recognized by 7H9D6 are located in clusters on the cell surface. In contrast, other CD44 antibodies produced a uniform staining pattern. Early bone marrow B cells were negative for 7H9D6 but reactive with other CD44 monoclonal antibodies. In contrast, leukaemic cells from 65% of patients (28 of 43) with B lineage acute lymphoblastic leukaemia bound 7H9D6. Patients expressing the 7H9D6 epitope on their leukaemic cells had an increased risk of death (HR 3.5 95% CI 1.1-10.9, P = 0.029) and of disease relapse (HR 3.2 95% CI 1.2-8.5, P = 0.017) when corrected for white cell count. This antibody may be useful for the detection of residual disease in B lineage acute lymphoblastic leukaemia and as a prognostic indicator and for the study of CD44 function.
先前的研究表明,抗体7H9D6可识别CD44,一种透明质酸的糖蛋白受体。7H9D6识别CD44的一个表位,该表位并非总是存在于CD44分子上。7H9D6抗体与CD44的透明质酸结合域结合,并抑制细胞与固定化透明质酸的黏附。然而,7H9D6表位的表达不足以实现透明质酸结合。用7H9D6进行免疫荧光染色显示出点状表面染色模式,表明被7H9D6识别的CD44分子位于细胞表面的簇中。相比之下,其他CD44抗体产生均匀的染色模式。早期骨髓B细胞对7H9D6呈阴性,但与其他CD44单克隆抗体有反应。相反,65%(43例中的第28例)B系急性淋巴细胞白血病患者的白血病细胞与7H9D6结合。白血病细胞上表达7H9D6表位的患者,校正白细胞计数后,死亡风险增加(风险比3.5,95%置信区间1.1 - 10.9,P = 0.029),疾病复发风险增加(风险比3.2,95%置信区间1.2 - 8.5,P = 0.017)。该抗体可能有助于检测B系急性淋巴细胞白血病中的残留疾病,并作为一种预后指标以及用于研究CD44的功能。