Valent Peter, Hadzijusufovic Emir, Grunt Thomas, Karlic Heidrun, Peter Barbara, Herrmann Harald, Eisenwort Gregor, Hoermann Gregor, Schulenburg Axel, Willmann Michael, Hubmann Rainer, Shehata Medhat, Selzer Edgar, Gleixner Karoline V, Rülicke Thomas, Sperr Wolfgang R, Marian Brigitte, Pfeilstöcker Michael, Pehamberger Hubert, Keil Felix, Jäger Ulrich, Zielinski Christoph
Ludwig Boltzmann Cluster Oncology, Vienna, Austria.
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Wien Klin Wochenschr. 2018 Sep;130(17-18):517-529. doi: 10.1007/s00508-018-1355-7. Epub 2018 Jul 13.
In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies. The LSC phenotypes were established in acute and chronic myeloid leukemia, in acute lymphoblastic leukemia and in chronic lymphocytic leukemia. In addition, the concept of preleukemic (premalignant) neoplastic stem cells (pre-L-NSC) was coined by the LBC ONC and was tested in myelodysplastic syndromes and myeloproliferative neoplasms. Phenotypic characterization of LSC provided a solid basis for their purification and for the characterization of specific target expression profiles. In a second phase, molecular markers and targets were validated. This second phase is ongoing and should result in the development of new diagnostics parameters and novel, more effective, LSC-eradicating, treatment strategies; however, many issues still remain to be solved, such as sub-clonal evolution, LSC niche interactions, immunologic control of LSC, and LSC resistance. In the forthcoming years, the LBC ONC will concentrate on developing LSC-eradicating strategies, with special focus on LSC resistance, precision medicine and translation of LSC-eradicating concepts into clinical application.
2008年，路德维希·玻尔兹曼肿瘤集群研究中心（LBC ONC）在路德维希·玻尔兹曼之前的两个从事血液学和癌症研究领域的研究所基础上成立。LBC ONC的总体目标是通过根除癌症起始细胞和疾病传播细胞（在白血病背景下也称为白血病干细胞，LSC）来改善造血系统肿瘤的治疗。在第一阶段，LBC ONC对各种恶性肿瘤中LSC的表型和分子畸变谱进行了表征。LSC表型在急性和慢性髓系白血病、急性淋巴细胞白血病和慢性淋巴细胞白血病中得以确立。此外，LBC ONC提出了白血病前期（癌前）肿瘤干细胞（pre-L-NSC）的概念，并在骨髓增生异常综合征和骨髓增殖性肿瘤中进行了验证。LSC的表型特征为其纯化以及特定靶标表达谱的表征提供了坚实基础。在第二阶段，分子标志物和靶标得到了验证。第二阶段仍在进行中，预计将产生新的诊断参数以及新的、更有效的根除LSC的治疗策略；然而，许多问题仍有待解决，例如亚克隆进化、LSC生态位相互作用、LSC的免疫控制以及LSC耐药性。在未来几年，LBC ONC将专注于开发根除LSC的策略，特别关注LSC耐药性、精准医学以及将根除LSC的概念转化为临床应用。
