B-Cell Precursor Lymphoma as a model for immune control, dissemination and low-risk subgroups of precursor cell neoplasms

前体B细胞(PBC)肿瘤是一种具有未成熟B细胞特性的疾病。由于恶性细胞通常可以在血液和骨髓中发现，这种疾病也被称为PBC白血病。然而，在一些患者中，恶性细胞发生在组织内(如淋巴结)，而不存在于血液和骨髓中。这些疾病被称为PBC淋巴瘤。由于以淋巴瘤为表现的疾病比以白血病为表现的疾病要罕见得多，因此PBC淋巴瘤几乎还没有得到分子水平的研究。然而，临床观察表明，PBC淋巴瘤可能具有不同于白血病的特性。与白血病相比，尤其是有限阶段的淋巴瘤疾病可以用更少的化疗来治愈。在基尔的血液病理科，我们能够收集过去几十年来世界范围内独特的PBC淋巴瘤集合。这是可能的，因为我们是照顾PBC淋巴瘤儿童的研究组(NHL-BFM研究组)的中央诊断单位。因此，我们是世界上仅有的能够对这种疾病进行有意义的分析的中心之一。对PBC淋巴瘤的研究必须采用与白血病部分不同的方法，因为含有恶性细胞的组织标本很小，而且包埋在蜡(石蜡)中。因此，我们开发了一套适用于这种生物材料的方法组合，并成功地将其应用于儿童的其他B细胞淋巴瘤，从而认识到儿童和成人疾病之间的差异。在申请的项目中，我们计划使用我们独特的PBC淋巴瘤组织收集来了解PBC淋巴瘤的分子特性。在初步实验中，我们测试了已知在PBC白血病中发生的最常见的染色体变化(易位)。有趣的是，与白血病相比，这些易位的频率在淋巴瘤中是不同的。这些第一个结果带来了希望，随着对淋巴瘤的预期更精确的分子分析以及与白血病的比较，我们将理解为什么这些疾病表现得如此不同。我们希望找到证据表明免疫系统是如何防止淋巴瘤中的肿瘤细胞在血液中扩散并将它们表现为白血病的。在合作研究小组中，我们可以将淋巴瘤的研究结果与白血病的研究结果相互关联。在多氯联苯白血病中寻找多氯联苯淋巴瘤的“分子对应物”的尝试与希望能够用更少的化疗来治疗一些白血病有关。

Precursor B-cell (PBC) neoplasms are diseases that have properties of immature B-cells. Because the malignant cells can usually be found in the blood and bone marrow, the diseases are also known as PBC leukemia. In some patients, however, the malignant cells are occur within the tissues (e.g. lymph nodes) and are absent from the blood and bone marrow. These diseases are known as PBC lymphomas. Since the presentation of the disease as lymphoma is much rarer than the presentation as leukemia, the PBC lymphomas have almost not been studied molecularly yet. However, clinical observations indicate that the PBC lymphoma may have properties distinct from leukemia. Particularly limited stages of the lymphoma disease can be cured with less chemotherapy than is the case for leukemia. In the Hematopathology Section in Kiel, we have been able to gather a worldwide unique collection of PBC lymphomas over the past decades. This was possible because we serve as the central diagnostics unit for the study group that cares for children with PBC lymphomas (NHL-BFM study group). As a result, we are one of the only centers in the world able to carry out meaningful analyzes of the disease. Research on PBC lymphomas has to apply methods differing in part from leukemia, because the tissue specimen with malignant cells is small and embedded in wax (paraffin). We have therefore developed a portfolio of methods suitable for this type of bio-material, successfully applied it to other B-cell lymphomas in children and thus recognized the differences between the diseases in childhood and adulthood. In the project applied for, we plan to use our unique tissue collection from PBC lymphomas to understand the molecular properties of PBC lymphomas. In preliminary experiments we tested for the most common chromosomal changes (translocations) known to occur in PBC leukemias. Interestingly, the frequency of these translocations is different in lymphoma compared to leukemia. These first result raise hope that with the intended much more precise molecular analysis of the lymphomas and the comparison with leukemia, we will understand why the diseases present themselves so differently. We expect to find evidence of how the immune system is preventing the neoplastic cells in lymphoma from disseminating in the blood and presenting them as leukemia. Within the collaborative research group, we can interrelate or results on lymphomas with findings in leukemia. The attempt to find a “molecular counterpart” of the PCB lymphomas among the PCB leukemias is linked to the hope of being able to treat some leukemias with less chemotherapy.