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）肿瘤是具有未成熟b细胞特性的疾病。因为恶性细胞通常可以在血液和骨髓中发现，所以这种疾病也被称为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），而不在血液和骨髓中。这些疾病被称为PBC淋巴瘤。由于该疾病以淋巴瘤的表现比以白血病的表现罕见得多，PBC淋巴瘤的分子研究几乎尚未完成。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。特别是在有限的阶段，淋巴瘤可以用比白血病更少的化疗来治愈。在基尔的血液病理学科，我们已经能够在过去的几十年里收集到世界范围内独一无二的PBC淋巴瘤。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）的中心诊断单位。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。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，并且包埋在蜡中。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年疾病之间的差异。在申请的项目中，我们计划利用我们独特的PBC淋巴瘤组织标本来了解PBC淋巴瘤的分子特性。在初步实验中，我们检测了已知发生在PBC白血病中最常见的染色体改变（易位）。有趣的是，这些易位的频率在淋巴瘤和白血病中是不同的。这些初步结果带来了希望，通过对淋巴瘤进行更精确的分子分析，并与白血病进行比较，我们将了解为什么这两种疾病的表现如此不同。我们希望找到免疫系统如何阻止淋巴瘤中的肿瘤细胞在血液中扩散并表现为白血病的证据。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联系起来。在多氯联苯白血病中寻找多氯联苯淋巴瘤的“分子对偶物”的尝试，与能够用较少的化疗治疗某些白血病的希望有关。

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.