Firkin F, Schneider H, Grill V
University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy, Australia.
Leuk Lymphoma. 1998 May;29(5-6):499-506. doi: 10.3109/10428199809050909.
Hypercalcemia is an important complication in multiple myeloma as well as T-cell leukemia/lymphoma, and is moderately common in high and intermediate grade non-Hodgkin's lymphoma. The underlying mechanism has been unclear because the neoplastic cells are usually present in the bone marrow, where they are in a position to produce short range effects on bone resorption which are difficult to identify. This contrasts with the situation in hypercalcemia associated with non-metastatic carcinoma, where it has been clearly demonstrated that the most common cause is release from the tumor of a humoral mediator, Parathyroid Hormone-related Protein (PTHrP). Roles have been advocated in multiple myeloma for release of a number of other cytokines with osteolytic capacity on the basis of their enhancement of osteolytic activity in cultured fetal rat bone, although a causal relationship in patients has not been established. PTHrP has more recently been implicated in the genesis of hypercalcemia in patients with hematological malignancies by the demonstration in a proportion of cases of increased circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer. Immunohistochemical studies indicate neoplastic hemopoietic cells can contain PTHrP, and thus have the capacity to act in a paracrine manner to enhance local bone resorption and contribute to the development of hypercalcemia.
高钙血症是多发性骨髓瘤以及T细胞白血病/淋巴瘤的重要并发症，在高中度非霍奇金淋巴瘤中也较为常见。其潜在机制一直不明，因为肿瘤细胞通常存在于骨髓中，在那里它们对骨吸收产生的局部效应难以识别。这与非转移性癌相关的高钙血症情况不同，在后者中已明确表明最常见的原因是肿瘤释放一种体液介质，即甲状旁腺激素相关蛋白（PTHrP）。基于多种具有溶骨能力的其他细胞因子在培养的胎鼠骨中增强溶骨活性，有人主张它们在多发性骨髓瘤中发挥作用，尽管尚未在患者中确立因果关系。最近，通过在一部分病例中证明循环中PTHrP水平升高，与癌症所致高钙血症中的水平相当，PTHrP被认为与血液系统恶性肿瘤患者高钙血症的发生有关。免疫组织化学研究表明，肿瘤造血细胞可含有PTHrP，因此有能力以旁分泌方式增强局部骨吸收并促进高钙血症的发展。
