Collaboration with Investigators from the Multiple Myeloma Section, Medical Oncology Branch, NCI and of the Molecular Medicine Branch, Molecular Genomics & Therapeutics Section, NIDDK

我们的研究集中在浆细胞癌患者骨髓的评价上。 正常的浆细胞（PC）产生免疫球蛋白（抗体），这是有助于对抗感染的有用蛋白质。 当PC变成癌症时，它们可能会导致严重的疾病。 典型的例子是多发性骨髓瘤（MM），这是一种目前无法治愈的癌症，它会破坏骨骼，损害骨髓中的血细胞形成，降低免疫力，并可能损害肾脏和神经。 这种疾病的严重程度在很大程度上取决于骨髓中肿瘤的数量。 目前正在详细研究MM及其前体，如闷烧骨髓瘤，并正在深入研究新的治疗方法。 我们在这些研究中的作用是利用最先进的实验室技术检查MM和相关疾病患者的骨髓，以确定骨髓中PC的数量和分布并表征其性质。 然后将这些观察结果与其他实验室和临床数据相关联，以确定这些癌症的临床行为及其对治疗的反应。 另一项合作研究包括检查从镰状细胞病（SCD）儿童中获得的培养红细胞，这是一种严重的红细胞遗传疾病，使它们改变形状并变得更加脆弱。 SCD患者的临床结局和对当前治疗的反应差异很大，迫切需要新的治疗方法。 在从这些患者中取出循环祖细胞（称为CD34+细胞）并插入编码命名为LIN28A的蛋白质的基因后，我们在培养物中观察到，与对照组相比，来自CD34+细胞的后代红细胞较少出现镰状细胞。使用这种方法或类似方法的进一步研究可能有助于开发SCD的有效疗法。

Our investigations centered on the evaluation of bone marrow from patients with plasma cell cancers. Normal plasma cells (PC) produce immunoglobulins (antibodies), useful proteins that help fighting infections. When PC become cancerous they may cause serious diseases. The typical example is multiple myeloma (MM), a currently incurable cancer that destroys bones, impairs blood cell formation in the marrow, decreases immunity and may damage kidneys and nerves. The severity of the disease largely depends on the amount of tumor within the bone marrow. MM and its precursors such as smoldering myeloma are currently studied in detail and new treatments are being investigated intensely. Our role in these investigations was to examine bone marrows from patients with MM and related disorders utilizing state-of- the-art laboratory techniques to determine the number and distribution of PC within the marrow and characterize their nature. These observations are then correlated with other laboratory and clinical data to determine the clinical behavior of these cancers and their response to therapy. Another collaborative study consisted on examining cultured red cells obtained from children with sickle cell disease (SCD), a serious genetic disorder of red cells that make them change shape and become more fragile. The clinical outcomes and response to current therapy among patients with SCD vary widely and new treatments are badly needed. After taking circulating progenitor cells (called CD34+ cells) from these patients and inserting a gene coding for a protein designated as LIN28A, we observed in cultures that the descendant red cells from the CD34+ cells were less frequently sickle cells in comparison to the controls. Further studies using this or a similar approach may contribute to develop effective therapies for SCD.