Table 1: Characteristics and results of selected studies.

Author Year of publication Study design Number of participants Neurological disease (HAM/TSP) Hematologic disease (ATL) Results
Fetchick et al. [48] 1986 Experimental (in vitro) - - Yes Production of 1,25(OH)2 D by lymphoma cells may contribute to the pathogenesis of the hypercalcemia in ATL.
Dodd et al. [54] 1986 Case series 5 - Yes Five patients with ATL had 1,25(OH)2D levels in or below the normal range and it was not associated with usual cause of hypercalcemia in such patients.
Nakao et al. [46] 1987 Experimental (in vitro) - - Yes 1,25(OH)2D inhibited the proliferation and de novo DNA synthesis of certain HTLV-positive T cell lines.
Kiyokawa et al. [53] 1987 Case series 18 - Yes 1,25(OH)2D level was low in two ATL patients with hypercalcemia. Hypercalcemia in ATL patients may be a result from the production by tumor cells of factor (s) stimulating osteoclastic bone resorption.
Reichel et al. [47] 1987 Experimental (in vitro) - - Yes HTLV-1-transformed lymphocytes can produce 1,25(OH)2D but the excess 1,25(OH)2D production was probably not associated in the pathogenesis of ATL-associated hypercalcemia.
Fukumoto et al. [51] 1988 Case series 10 Yes ATL patients with hypercalcemia had low levels of 1,25(OH)2D.
Koizumi et al. [42] 1989 Experimental (in vitro) - - Yes 1,25(OH)2D and glucocorticoid inhibited the cellular proliferation and c-myc mRNA expression in HTLV infected T-cell-line KH-
2 cells.
Yamada et al. [41] 1991 Experimental (in vitro) - Yes - Three of the four cell lines from HAM/TSP patients had their de novo DNA synthesis inhibited by steroid hormones (dexamethasone and 1,25(OH)2D) and cyclosporin A. This inhibition of cellular proliferation was not caused by the inhibition of HTLV p40 gene but by inhibition of transcriptional factors such c-myc products.
Umemiya-Okada et al. [56] 1992 Experimental (in vitro) - - Yes The expression of leukemia inhibitory factor (LIF) mRNA was suppressed by 1,25(OH)2D and dexamethasone in HTLV-1-infected T-cell lines. The expression of the LIF gene was associated in the development of hypercalcemia in ATL.
Johnston et al. [52] 1992 Case report 1 Yes Elevated serum levels of 1,25(OH)2D and parathyroid hormone-related protein (PTHrP) were demonstrated in a patient with ATL hypercalcemia.
Inoue et al. [43] 1993 Experimental (in vitro) - - Yes 22-oxa-1,25(OH)2D3 (noncalcemic analogue) and 1,25(OH)2D suppressed both cell proliferation and PTHrP gene expression through binding to the vitamin D receptor overexpressed in HTLV-1-infected T cells.
Elstner et al. [44] 1994 Experimental
(in vitro)
- - Yes 1,25(OH)2-20-epi-D3, the potent 1,25(OH)2D analog, was identified with antiproliferative and differentiating effects on leukemic cells.
Seymour et al. [50] 1994 Case report 1 - Yes Hypercalcemia with normal PTHrP and vitamin D levels.
Peter et al. [49] 1995 Case report 2 - Yes Hypercalcemia with normal vitamin D levels. PTHrP seems to be the supposed factor for the hypercalcemia associated with ATL.
Saito et al. [40] 2005 Cross-sectional 207 patients with HAM/TSP and 224 asymptomatic carriers Yes - ApaI polymorphism of vitamin D receptor (VDR) was associated with the risk of HAM/TSP, although this polymorphism did not affect the proviral load of HTLV-1 in either HAM/TSP patients or asymptomatic HTLV-1 seropositive carriers.
Masutani H et al. [57] 2005 Review - - Yes Thioredoxin binding protein-2 (TBP-2)/vitamin D3 upregulated protein 1 (VDUP1) was a growth suppressor and its expression was suppressed in HTLV-1-transformed cells.

Back to Article