The etiology and pathogenesis of leukemia

Genetic theory. This theory deserves special attention, as there is a prevalence of HP in separate families, in particular in identical twins. The fact that patients with leukemia parents usually give birth to healthy children, does not contradict genetic (hereditary and congenital) theory as HP, apparently, is a disease with a small hereditary penetrance.
In genetic terms have the meanings revealed in the last time abnormal karyotypes in Leningrad In chronic myeloid leukemia is known there is a defect in the 21st pair of chromosomes (the"Philadelphia chromosome-Ph'), the essence of which consists in decrease (about 1/3) of the substance of the long arm of the chromosome. In addition, with down syndrome, in which is found trisomy also on the 21st pair of chromosomes, acute leukemia occurs in 20 times more frequently than in normal cases. In General karyotype acute L. are not sufficiently specified: changes set mainly through decrease or increase the modal number of chromosomes. With an abnormality of chromosome apparatus is connected and the breach of the production of certain chemical agents (enzymes)that are necessary for cell metabolism. For example, the lack of alkaline phosphatase in chronic myeloid leukemia associated with the "Philadelphia chromosome.
Genetic theory of leukemia does not contradict the fact that some forms of leukemia (lymphocytic leukemia, myeloma, eritremia) met with mostly after 40 years; after all, and this is clearly a congenital disease, such as pernicious anemia, firstly detected also in the middle or old age. Assume that people predisposed to the disease HP, until a certain period of life can be supported by compensatory mechanisms (possibly develop inhibitors of disturbed currency). Clinical becoming L. related to exogenous and endogenous factors leading to cell mutations, and, finally, L. develops only in the progression of disorders of cell metabolism to the stage of formation of substances having blastomogenic (leucotaenium) action. Thus, by analogy with the concept of polyetiological neoplastic diseases (N. N. Petrov) leukemia can be considered the consequence of not one cause, and the whole complex of endogenous and exogenous factors.
From the recognition of tumorous L. it follows that the systematic destruction of the body when L is formed not through the development of metastases in the bodies, as it is typical of malignant tumors, and by autochthonous "blood" in the reticular stroma bodies. This is the peculiarity blastomere morphogenesis L. and their difference from malignant tumors.
The concept of the focuses of blood when leukemia is conditional, as they reproduction immature cells is by lowering their capacity to differentiate and therefore correct to speak about leukemia infiltrates.
Peculiarities of metabolism processes in HP manifested mainly in the form of deep metabolic tryptophan (appearance in the urine of large quantities of intermediate products exchange of this amino acid and vitamin B6). Some metabolites of tryptophan (3-Oxandrolone acid, 3-oxichinolinr, resulting in the transformation of tryptophan to Niacin, and indole, indican, 3-indolyl-acetic acid and 5-methyltryptamine) are themselves leucosolenia, as with their help the animals may be obtained by different models of L. Occurring in patients with leukemia, the accumulation of these intermediates, apparently, prevents the normal use of tryptophan for protein synthesis. Assume that when HP has been a violation of nucleotide metabolism in the cells. On the basis of cytochemical research can only speak about the difference in the content of RNA in normal and leukemic cells.