%0 Journal Article
%T Pathogenesis of Metastatic Calcification and Acute Pancreatitis in Adult T-Cell Leukemia under Hypercalcemic State
%A Masachika Senba
%A Kioko Kawai
%A Naoki Mori
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/128617
%X Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). Hypercalcemia is common in patients with ATL. These patients rarely develop metastatic calcification and acute pancreatitis. The underlying pathogenesis of this condition is osteoclast hyperactivity with associated overproduction of parathyroid hormone-related protein, which results in hypercalcemia in association with bone demineralization. The discovery of the osteoclast differentiation factor receptor activator of nuclear factor-¦ÊB ligand (RANKL), its receptor RANK, and its decoy receptor osteoprotegerin (OPG), enhanced our understanding of the mechanisms of ATL-associated hypercalcemia. Macrophage inflammatory protein-1-¦Á, tumor necrosis factor-¦Á, interleukin-1, and interleukin-6 are important molecules that enhance the migration and differentiation of osteoclasts and the associated enhanced production of RANKL for osteoblast formation. In this paper, we focus on metastatic calcification and acute pancreatitis in ATL, highlighting recent advances in the understanding of the molecular role of the RANKL/RANK/OPG system including its interaction with various cytokines and calciotropic hormones in the regulation of osteoclastogenesis for bone resorption in hypercalcemic ATL patients. 1. Introduction Adult T-cell leukemia (ATL) was first reported as a new clinical entity in 1977 in Japan [1, 2]. The predominant physical findings are skin involvement, such as erythroderma and nodule formation due to the infiltration of neoplastic cells, lymphadenopathy, and hepatosplenomegaly. The ATL cells are of mature T-helper phenotype and have a characteristic appearance with especially indented or lobulated nuclei. Hypercalcemia is common in patients with ATL, and such patients often show increased numbers of osteoclasts. A type C retrovirus was isolated from patients with cutaneous T-cell lymphoma by Poiesz and colleagues in 1980 [3]. This virus was later renamed human T-cell leukemia virus type 1 (HTLV-1). In 1981, Hinuma et al. [4] and Yoshida and colleagues [5] reported the isolation of a type C retrovirus named adult T-cell leukemia virus. The two isolates of human leukemia virus, HTLV-1, and adult T-cell leukemia virus, were later confirmed to be the same species of human retrovirus HTLV type I (US isolate) and ATLV (Japanese isolate) [6]. Approximately 16 to 20 million people are infected with HTLV-1 worldwide, and 1 to 5% of the infected individuals develop ATL during their lifetime [7] caused by the transformation of their CD4+ T cells [8]. In Japan, it is
%U http://www.hindawi.com/journals/lrt/2012/128617/