The role of cadmium in the pathogenesis of myeloid leukemia in individuals with anemia, deficiencies in vitamin D, zinc, and low calcium dietary intake

J Trace Elem Med Biol. 2023 Sep:79:127263. doi: 10.1016/j.jtemb.2023.127263. Epub 2023 Jul 16.

Abstract

Iron deficiency, vitamin D deficiency and low calcium diet are frequent health problems with severe long- term consequences. Upon absorption from the duodenum, cadmium binds to transferrin, and cells with the highest density of transferrin receptor 1 (TfR1) take up the majority of the circulating cadmium. Nowadays, it is clear that individuals with iron deficiency anemia have increased blood levels of cadmium because of higher absorption rate, mediated by divalent metal transporter 1 (DMT1). However, the transient receptor potential vanilloid receptor 6 (TRPV6), known as a calcium carrier, is able to bind and transport cadmium as well. In the case of low calcium diet or vitamin D deficiency, TRPV6 may be overexpressed in the intestine and kidney tubules and absorbs (re-uptake in the case of renal tubules) cadmium in larger quantities, resulting in an increased cadmium blood levels. We speculate that the final event in the case of low calcium dietary diet and/or vitamin D deficiency is similar to what is observed in the case of iron deficiency, that cells with the highest levels of TfR1 (for example, megakaryocyte/erythrocyte progenitors and pro-erythroblasts) take up most of the circulating cadmium, which is powerful malignancy inductor, leading to appearance of acute myeloid leukemia (AML).

Keywords: AML; Calcium; Iron deficiency; TRPV6.

Publication types

  • Review

MeSH terms

  • Anemia*
  • Cadmium / metabolism
  • Calcium / metabolism
  • Eating
  • Humans
  • Iron / metabolism
  • Iron Deficiencies*
  • Leukemia, Myeloid*
  • Transferrin
  • Vitamin D
  • Vitamin D Deficiency*
  • Vitamins
  • Zinc / metabolism

Substances

  • Cadmium
  • Calcium
  • Zinc
  • Iron
  • Vitamin D
  • Transferrin
  • Vitamins