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Over‐expression of CCL3 MIP‐1α in a blastoid mantle cell lymphoma with hypercalcemia
Author(s) -
Hattori Norimichi,
Nakamaki Tsuyoshi,
Ariizumi Hirotsugu,
Homma Mayumi,
YamochiOnizuka Toshiko,
Ota Hidekazu,
Tomoyasu Shigeru
Publication year - 2010
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2009.01405.x
Subject(s) - mantle cell lymphoma , rankl , medicine , cancer research , parathyroid hormone , lymphoma , endocrinology , receptor , activator (genetics) , calcium
We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL‐BV), a rare subtype of B‐cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme‐linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1α (MIP‐1α), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone‐related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT‐PCR) analysis, we found predominant expression of mRNA for MIP‐1α in addition to those for receptor‐activator of nuclear‐factor kappa B ligand (RANKL), TNF‐α, and IL‐6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP‐1α significantly stimulated 3 H‐thymidine uptake by isolated MCL cells in vitro . Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP‐1α. In the present case, MIP‐1α, an osteoclast‐activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T‐cell leukemia/lymphoma (ATLL). Furthermore, MIP‐1α is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP‐1α is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B‐cell lymphoma.