Bühring H J, Sures I, Jallal B, Weiss F U, Busch F W, Ludwig W D, Handgretinger R, Waller H D, Ullrich A
Second Department of Internal Medicine, University of Tübingen, Germany.
Blood. 1995 Sep 1;86(5):1916-23.
The class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B-lymphoblastic leukemias.
I类受体酪氨酸激酶（RTK）HER2是一种癌蛋白，经常参与上皮源性肿瘤的发病机制。在此，我们报告了健康供体外周血和骨髓细胞、造血细胞系以及急性淋巴细胞白血病（ALL）、急性髓细胞白血病（AML）、慢性淋巴细胞白血病（CLL）和慢性髓细胞白血病（CML）患者白血病原始细胞中的mRNA表达情况。然而，HER2蛋白（p185HER2）的细胞表面表达仅在B淋巴细胞系白血病细胞亚群中发现。在15例婴儿样本中的2例、19例成人C-ALL（CD19+CD10+）患者样本中的9例以及2例前B-ALL（CD19+CD10-）患者样本中的1例的原始细胞上发现了p185HER2表达，而AML（0/30）、T-ALL（0/7）、CLL（0/5）（CD19+CD5+）患者的白血病细胞，以及慢性期和加速期CML（0/5）或髓系分化的急变期CML（0/1)4患者的白血病细胞均未检测到p185HER2阳性。然而，4例B淋巴细胞急变期CML（CD19+CD10+）患者中的3例的细胞表达高水平的p185HER2，在CML来源的B细胞系BV-173和Nalm-1表面也发现了p185HER2。我们的研究首次显示了造血来源恶性细胞上p185HER2的表达。这种致癌性受体酪氨酸激酶在造血细胞类型中的异常表达可能是导致一部分B淋巴细胞白血病发生的致癌事件。
