Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.

Low-density lipoprotein receptor-related protein 1 (LRP1, also known as CD91), a multifunctional endocytic and cell signaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, ifbroblasts, neu-rons, astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging invitro and invivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. For example, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase (MMP)-2 and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor, the serine/threonine protein kinase signaling pathway, and the expression of Caspase-3. LRP1-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation ofLRP1 CpG islands. Furthermore, a novel fusion gene,LRP1-SNRNP25, promotes osteosarcoma cell invasion and migration. Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

pGEX-e23 (scFv) PE40融合基因的构建及其在大肠杆菌中的表达

目的　在大肠杆菌中表达抗原癌基因c-erbB-2表达产物p185的单 链抗体e23(scFv)/假单孢菌属外毒素活性片 段PE40免疫毒素的融合蛋白，为乳腺癌、胃癌等多种c-erbB-2呈过量表达的恶性肿瘤的免疫治疗奠定基础. 方法　去除克隆在真核表达载体pLNCX中的e23 (scFv) PE40基因5′端编码信号肽的核苷酸序列，并将改建后的融合基因克隆到原核融合表达载体pGEX-4T中表达. 结果　序列测 定 表明. 改建后的抗p185 e23(scFv)/PE40序列正确. 融合基因经IPTG诱导表达4 h后，经SDS -聚丙烯酰胺凝胶电泳分析，在Mr 90 000处出现一条新生蛋白带，表达量约占菌体总蛋白的15%. 结论　成功改建并在原核中表达了抗p185 e23 (scFv)/ PE40融合蛋白.