Effects of vitamin D on the growth of normal and malignant B-cell progenitors

Abstract

SUMMARYAs the effects of vitamin D 3 , 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 -D 3 ) (VD, calcitriol) on the proliferation and differentiation potential of normal and leukaemic cells in vitro of myeloid lineage are known, we investigated the response to VD on the growth of both normal and malignant lymphoid progenitors. Effects of vitamin D on normal human lymphoid progenitors and B lineage acute lymphoblastic leukaemia (ALL) progenitors were assessed by using an in vitro cell colony assay specific for either B or T cell lineages. The expression of VDR on B untreated malignant progenitors at diagnosis was investigated by RT-PCR analysis. VD induced a significant inhibition of normal lymphoid cell progenitors growth of both T and B lineage. VD inhibited significantly also the growth of malignant B cell lineage lymphoid progenitors, without inducing cytotoxic effect. As it has been reported that VD effects on activated lymphocytes are mediated by 1,25-(OH) 2 -D 3 nuclear receptor (VDR), we investigated VDR expression on malignant B cell progenitors. We did not detect VDR expression on these cells examined at diagnosis. We demonstrated that VD inhibited in vitro the clonogenic growth of both normal and malignant lymphoid B cell progenitors and that this inhibitory effect on malignant B cell progenitors was not related to VDR. Our work contributes to understanding of the mechanism of action of this hormone in promoting cellular inhibition of clonal growth of malignant lymphoid B cell progenitors, suggesting that the regulation of some critical growth and differentiation factor receptors could be a key physiological role of this hormone.

Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts

“…30 The expression of these molecules on PEL cells was confirmed by immunohistochemical staining (Figure 4).…”

“…First, cross-linking of the adhesion molecule PSGL-1 has been described to inhibit proliferation of hematopoietic stem cells, 43 implying a potential functional role for this surface receptor also in the control of cell proliferation. Second, because it has been suggested for other vitamin D 3 receptor-positive B-cell malignancies, 30 activation through the vitamin D 3 receptor exposed on PEL cells might induce differentiation of the tumor cells and potentially contribute to treatment. Third, PEL tumor cells express mucin-1, a tumorassociated antigen that might represent a suitable target for antibody-mediated therapy.…”

Vitamin D in hematological disorders and malignancies

“…In another type of NHL, DLBCL, treatment of the cell line models with calcitriol and vitamin D analogs induced necrosis . Calcitriol also inhibits growth of malignant B cell progenitors from ALL, while leaving viability and differentiation state unchanged .…”

Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia

“…In addition, Antony et al [] showed that 1,25D had no effect on lymphoblastic leukemia cell proliferation, and actually had a modest effect of impairing dexamethasone cytotoxicity and induction of apoptosis. On the contrary, Consolini et al [] reported significant inhibition of the growth of normal and malignant lymphoid progenitors by 1,25D, despite lack of detectable VDR expression on leukemic blast cells, suggesting a leukemia cell‐extrinsic function of 1,25D in regulating leukemogenesis. Considering the tightly controlled yet multifactorial variability in these in vitro experiments, further detailed investigations into leukemia cell‐intrinsic and ‐extrinsic effects of VDDs in the physiologically relevant in vivo setting of human malignancies and animal models are strongly warranted.…”