Causes Leukemia

The question of the etiology Leukemia, as well as other tumors, It boils down to the definition of inherited or acquired conditions, contributing to the emergence of tumors, one side, and to clarify the immediate causes, unlimited calling cell proliferation of one of the - the other.

In the group of leukemia tumor found, naturally occurring under the influence of the obvious mutagens (Some acute leukemia, Chronic myelosis), and tumors, not induced by them (chronic lymphoproliferative processes), but often inherited.

The role of ionizing radiation in the event of Leukemia

Analysis of radiation causes leukemia has shown, that there is a clear relationship between the frequency of chronic myeloid leukemia, acute myeloid leukemia, acute erythremic myelosis, acute lymphoblastic leukemia of childhood on the dose of ionizing radiation.

With all these leukemia proved the possibility of the direct involvement of radiation damage to chromosomes in tumor development, because the cells, substrate components of the tumor, We had specific radiation damage. At the same time we found an association frequency induced leukemia and age irradiated:

• lymphoblastic acute leukemia occurs under the influence of radiation in people younger than 19 years;
• Myeloid - mainly in the irradiated aged 30-44 years;
• Chronic myelosis also quickens in persons, irradiated at the age of 30-44 years, though, Besides, rise in incidence observed in children under the age of 9 years.

The role of chemical mutagens in the emergence of Leukemia

The possibility of increasing the frequency of leukemia among, exposed to benzene, It is known for a long time.

It was a logical assumption, that other factors are chemical mutagens and induces leukemia. However, the facts began to accumulate only recently, when they started to publish data on previously observed cases of acute myeloid leukemia (or acute leukemia myelomonoblastic, or acute erythremic myelosis) in patients with chronic lymphoid leukemia (chronic lymphocytic leukemia, multiple myeloma, Waldenstrom's macroglobulinemia) in the treatment of cytotoxic drugs.

In this form of myeloid or acute leukemia myelomonoblastic, induced by cytostatics (eg, 6-mercaptopurine, chlorambucil in rheumatoid arthritis), quickens even children, which usually myeloid leukemias are rare.

At the same time it showed a significant increased frequency of acute leukemia nelimfoblastnyh and chronic myeloid leukemia in the combined use of some cytotoxic drugs and radiation.

So called secondary leukemias, t. it is. caused by the action of cytostatic agents, or combinations thereof with irradiation, differ from those of acute leukemia nelimfoblastnyh rare remissions, speed flow and lack of leukemic cells 5 and (or) 7-of chromosomes or deletion.

The role of viruses in causing Leukemia

Currently, there is a large experimental data on the possible viral nature of leukemia in animals. During experimental studies of this problem have been identified viral oncogenes - genes, capable of continuously causes cells to proliferate after the insertion into its genome. The identity of the viral oncogenes cell, detected in tumor cells (including leukemia) animals and humans, It gives reason to believe, one side, Feedback oncogenes to tumor growth, on the other - how some viruses leykozogenezom.

So, Burkitt's lymphoma is possible with a certain degree of probability say about the role of Epstein-Barr virus in carcinogenesis as a factor, provoking an increased proliferation of lymphatic cells, conditions in which they arise specific mutations, lead to the development of lymphoma. Changed chromosomes, as it turned out, initially directly related to the lymphatic tissue, in which the tumor develops. This proves mutation, rather than the infectious nature of Burkitt's lymphoma, its dependence on the development of damage to specific chromosomes, by activation of specific genes which. These genes when transferring in vitro produce a tumor.

There is no reason to deny the possible role of the virus as a mutagen in leykozogeneze, but this must be confirmed, as a mutagen virus is not a specific etiologic factor. In favor of the viral nature of leukemia cases show the so-called horizontal proliferation of leukemia in some families, When leukemia (often different!) ill non-blood relatives or neighbors. The explanation of such phenomena from the perspective of infection seems to be the easiest. But we should not exclude the possibility of exposure to mutagenic agents (telluric radiation and chemical mutagens).

It does not definitively clarified the role of the virus in relapsed leukemia cells transplanted from the donor bone marrow in patients with acute leukemia (and remission), chronic myelosis. Since the form of leukemia and type of chromosome rearrangement Reserved, then, probably, it is a DNA transfer leukemic cells (transforming gene) into the genome of the donor cell in vitro.

The role of heredity in the occurrence of Leukemia

Leukemia can arise in families, which we have seen a similar form of leukemia patients, account genetic defects with or without modification of chromosomes.

Of particular interest are genetic diseases, which themselves have no relation to tumor processes, but predispose to leukemia. First of all, it is the disease with spontaneous chromosome breaks, nondisjunction somatic or sex chromosomes: Down's syndrome, Fankoni (nefronoftiz), Bloom syndrome, Klaynfeltera, Ternera, disease nondisjunction 8, 9-and or 13, 14-nd chromosome pairs etc..

When Bloom syndrome, Fanconi disease, which are characteristic of spontaneous chromosome breaks, uchaschenye described ostrыh myeloydnыh leykozov.

In families with hereditary chromosomal defects, especially when nondisjunction (congenital acromicria, Klinefelter's syndrome, and others.), there are cases of acute myeloid leukemia or chronic myeloid leukemia have more members, t. it is. Leukemia can be a family member, having no visible defects of chromosomes.

Leukemia cells from precursor lymphopoiesis often develop in hereditary diseases, are associated with the immune defect; laboratory detectable chromosomal instability there may not be observed.

In families, where there are hereditary defects immunity, describes the so-called family lymphatic leukemia and lymphosarcoma nature. Such cases are the proof, that inherited not the tumor, and genetic defects of those cells, of which develops a tumor.

Analysis of etiological factors leykozogeneza shows, that the occurrence of leukemia can be caused by external factors or predominantly, or endogenous predisposition, or a combination of both - all factors, not the cause leukemia, Mutable and increased in the tissue, to which they affect and in which the tumor develops in the future.

Analysis of conditions, contributing to the development of leukemia, results of cytogenetic studies, reveal part of chromosomal changes in the leukemia cells, Experiments on transfer of DNA from the cells in the normal, leading to its malignant transformation, Leukemia development process in accordance with the laws of tumor progression - all this testifies, leukemias that have a genetic, mutational basis. At the same time we are talking about specific individual forms of leukemia mutations, relating to specific chromosomes and specific areas in which, t. it is. certain genes, responsible for cell proliferation, one side, and the individual stages of differentiation of specific germs in hematopoiesis - the other. These specific mutations occur only under conditions of increased non-specific non-neoplastic cells has mutabelnosti, caused by any action of radiation, or chemical factors, or viral infections, any hereditary diseases or hereditary defects of hematopoietic tissue. In turn, instability of tumor genotype, characterizing already arisen mutant tumor cells, It leads to repeated mutations, Determining the autonomous selection of subclones and tumor progression.

Thus, development of leukemia can be represented schematically as a chain of events, beginning on the preceding stage of leukemia increased mutabelnosti normal hematopoietic cells, latentnogo period, during which in one of these cells and appears specific mutation activates specific gene (or genes), leading to the appearance of tumor cells, its boundless monoclonal proliferation, means the development of benign stage of leukemia in some of the blood-forming processes. Then in tumor cells is repeated mutation and selection of specifically mutated independent subclones, leading to the formation and progression of cancer.

Clone Origin Leukemia

Confirming the role of mutations in the origin of a number of leukemias and gematosarkom is good reason for the idea, that leukemia cells are a clone - the offspring of a single mutated cells and carry the signs originally mutated cells.

Chromosomal analysis of acute leukemia, eritremii occurred in patients for the treatment of radioactive phosphorus, revealed unambiguous in some cases, specific chromosomal changes in cancer cells (eg, ring chromosomes). This is a direct result of radiation exposure, and evidence of mutational nature of these forms of acute leukemia, their origin from a single cell.

When secreting immunoglobulins lymphocytoma, lymphosarcoma, multiple myeloma, Waldenstrom's macroglobulinemia - hemoblastoses, encountered in the lymph and plasma cells, revealed a sharp increase in any one immunoglobulin (electrophoregram to serum proteins, it forms a narrow band - M-gradient). This indicates the homogeneity of tumor cells in each case in protein synthesis and their origin from a single cell. When defeat the entire system lymphatic cells in the blood would increase the content of all types of gamma globulin, produced by these cells, rather than one species, and stripes on electrophoregram would be broad.

In chronic lymphocytic leukemia and leukemic cells detected uniformity in each case on the surface and cytoplasmic immunoglobulin.

These data suggest, that the basis of leukemia is not a perversion of activities throughout the hematopoietic system, no violation of the maturation of healthy cells, and the emergence of a first, and then (from her) a plurality of tumor cells - leukemic clone.