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

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6504
• Main Authors: Marchwicka, Aleksandra, Nowak, Kuba, Satyr, Anastasiia, Wołowiec, Dariusz, Marcinkowska, Ewa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.03.2023; MDPI
• Subjects: 1,25-dihydroxyvitamin D; Aged; Analysis; Antimicrobial peptides; Blood; blood cells; Blood Cells - pathology; Bone marrow; Cancer; CD14 antigen; Cell cycle; Cell Differentiation; Cell division; Cell proliferation; Ceruloplasmin; Chemokines; Chemotherapy; Differentiation; Dihydroxycholecalciferols; exon; Genes; Genetic transcription; Genomes; Genomics; Hematologic Neoplasms; Hematology; Humans; Immortalization; Immune response; Immune system; Immunotherapy; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukocytes; Leukocytes - pathology; Ligands; Malignancy; Mutation; Patients; sequencing; transcription; Transcriptomes; Tumor necrosis factor-TNF; Vitamin D; vitamin D receptor; Vitelline membrane; Poland; transcription; 1,25-dihydroxyvitamin D; blood cells; vitamin D receptor; immunity; hematological malignancy; exon; sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076504

(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 (cathelicidin antimicrobial peptide), (ceruloplasmin), (C-X-C motif chemokine ligand 9), (CD14 molecule) or (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.