Cancer Incidence Rate and Death Rate in Reverse Cardio-Oncology Are Controlled by the Variance of the Natural Level of CD34 Lymphopoietic Stemness in Different Normal Organs
According to RNA markers from Human Protein Atlas, the averaged CD34 stemness together with CD31 vascularity dominates in 12- and 4-folds over the immune marker of T-cells CD2 in eighteen normal tissues. The different levels of natural CD34 stemness in tissues directly determine the incidence rate of cancer in them, as well as the cancer mortality rate, but inversely. The level of reverse cardio-oncology, i.e., an increase of specific cancer hazard rate in patients with existing cardiovascular diseases (HRCVD), is determined by the level of CD34 stemness of the target tissue too, but inversely. A transition from a normal to a registered malignant state of tissue is accompanied by rapid (in a few months) quantitative substitution of natural CD34 stemness with myelopoietic PODXL2 stemness, which is recognized as a predictor of multimorbidity and mortality, and the “proteomic age clock.” The rapid transition of CD34 into PODXL2 stemness during malignization, which is also common for CVD and other severe illnesses, resembles a natural irreversible aging process, but is accelerated nearly tenfold. An overexpression of myelopoietic PODXL2 is secondary, originating from CD34 loss. Contributing to atherosclerosis and other cardiovascular diseases, PODXL2 is unable to reproduce lymphatic vessels and lymphocytopoiesis in the bone marrow. The primacy of CD34 loss, as the only and limited source of the lymphoid lineage of hematopoiesis, defines it as a real “shagreen skin” of life, as opposed to PODXL2, and in full accordance with the cause of radiation death of mammals. Accelerated aging is followed by an increase in the neutrophil-to-lymphocyte ratio (NLR) in blood, and an outstripping attrition of telomere length in lymphocytes compared with granulocytes. The rapid pathological increase in PODXL2 stemness in malignant tissues mimics a slower natural aging. It is also accompanied by a 3-6-fold acceleration of Ki67 reproductive activity in tissues for cell repair and regeneration not only in malignant tissues but in normal ones as well, which are injured lethally and sub-lethally during cytotoxic therapy. Thus, premature aging, i.e., 2-5-10 years survival in oncology, is controlled by the volume of the natural resource of CD34 stemness in specific tissue, which manages the delay of metastasis. The product of the current numbers of CD34 hematopoietic stem cells and their mean Hayflick’s limit is recommended as a measure of the current vital resource of the patients. This approach could reduce the wide range of
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