– it is not known where and how both stages (initiation and promotion) of the “birth” of a malignant stem cell take place. It is supposed, in the area of intensive proliferation of cells;
– also it is not known what process underlies the “birth” of a malignant stem cell. It is supposed that a normal somatic proliferating cell transforms into the malignant stem cell;
– the mechanism of the “birth” of a malignant stem cell is not known. It is supposed that following the carcinogenic impact the genotype and epigenetic changes of a normal proliferating somatic cell take place, and these are a launching mechanism for its transformation into the malignant stem cell;
– a malignant focus starts with the “birth” of one malignant stem cell (in 80% cases), two or more malignant stem cells (20%), which then form a clone of malignant cells;
– the malignant process is manifested through forming the primary malignant focus, which can be located in different organs and tissues, and it increases by proliferation of cells, appositional and invasive growth;
– the malignant process is developed by the haematogenous and lymphogenous spread in the host body while forming the secondary foci – metastases;
– the malignant process impacts haemopoiesis, homeostasis, immunity etc.
Thus, the contemporary notions:
1. The difference between haemoblastosis (leucosis and lymphoma) on the one hand and solid tumours on the other, is in the mechanism of the “birth” of a malignant stem cell;
– in the case of haemoblastosis, following the carcinogenic impact the genotype and epigenetic changes of a pluripotent or unipotent stem cell of myelo- or lymphopoiesis, a block of differentiation and its transformation into a malignant stem cell take place;
– it is supposed that in the case of solid tumours, following the carcinogenic impact genotype and epigenetic changes of a normal proliferating somatic cell take place, which are a launching mechanism for its transformation into a malignant stem cell.
2. The difference between leucosis on the one hand and lymphoma and solid tumours on the other, is in the manifestation of the malignant process:
– in the case of leucosis, the disease manifests itself by the affection of the red marrow, but the primary malignant focus is not formed. The “birth” of a malignant stem cell requires 2-4 genotype alterations of the nuclear DNA of a pluripotent or unipotent stem cell of myelo- or lymphopoiesis. Epigenetic alterations are of secondary importance, that is why changes in the living conditions and microenvironment of the precursor are not a prerequisite;