Casnici C, Volpe G, Lattuada D, Crotta K, Kuka M, Panuzzo C, Mastrotto C, Tonon G, Fazio V M, Saglio G, Marelli O
Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy.
Cancer Lett. 2009 Apr 8;276(1):61-7. doi: 10.1016/j.canlet.2008.10.032. Epub 2008 Dec 4.
New, potentially tumor-specific antigens have been described in Bcr/Abl positive leukemias. Besides the main BCR/ABL hybrid fusion transcripts, a small number of transcripts derived from alternative splicing between BCR exons 1, 13, and 14 with ABL exons 4 and 5 have been identified. These variants are expressed in chronic myelogenous leukemia and acute lymphocytic leukemia patients. The transcriptional products were characterized at their C-terminus by a large amino acid portion derived from out of frame (OOF) reading of the ABL gene. This OOF peptide is expressed only in leukemic cells and has no homology with known human proteins. In order to study an in vivo model, three 39-amino acid peptides, each corresponding to a third of the whole human OOF peptide sequence, were tested for their capacity to elicit specific immune responses in HLA A2.1 transgenic mice. Peptides A and B, but not C, induced the production of specific antisera, while A and C induced the generation of specific cytotoxic T lymphocytes.
在Bcr/Abl阳性白血病中已发现了新的、可能具有肿瘤特异性的抗原。除了主要的BCR/ABL杂交融合转录本外，还鉴定出了少数源自BCR外显子1、13和14与ABL外显子4和5之间选择性剪接的转录本。这些变体在慢性粒细胞白血病和急性淋巴细胞白血病患者中表达。转录产物在其C末端的特征是来自ABL基因移码（OOF）阅读的一大段氨基酸。这种OOF肽仅在白血病细胞中表达，与已知的人类蛋白质没有同源性。为了研究体内模型，测试了三种39个氨基酸的肽，每种肽对应整个人类OOF肽序列的三分之一，以检测它们在HLA A2.1转基因小鼠中引发特异性免疫反应的能力。肽A和B而非肽C诱导产生特异性抗血清，而肽A和C诱导产生特异性细胞毒性T淋巴细胞。
