Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States

Abstract

(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.

Keywords: 1,25-dihydroxyvitamin D; blood cells; exon; hematological malignancy; immunity; sequencing; transcription; vitamin D receptor.

Figure 1

Venn diagrams presenting differentially expressed genes. The overlap between the genes that are upregulated (a) or downregulated (b) after exposure to 1,25D of the cells from healthy volunteers and from patients. Figure 1 was prepared using an online tool available at https://bioinformatics.psb.ugent.be/webtools/Venn/ (accessed on 26 March 2023).

Figure 2

Expression of CYP24A1 in leukocytes from all individuals. Leukocytes from healthy volunteers and blasts from patients were ex vivo exposed to a vehicle or 10 nM 1,25D for 96 h. Then the mRNA was isolated, transcribed to cDNA and sequenced. The background expression (a) and the change in expression of CYP24A1 between 1,25D-treated sample in comparison to vehicle-treated sample (b) were presented as a dot for everyone. The graph presents means ± SEM and the values obtained for everyone. Values that differ significantly between patients and healthy people are marked with whiskers and asterisks.