The etiology and pathogenesis of human leukemia are still not fully understood. The known causes include infectious factors, ionizing radiation, chemical substances, genetic factors and abnormal immune function. It is currently believed that the cause of leukemia is the result of the interaction of the above factors.
First, radiation damage ionizing radiation leukemia effect has been confirmed in animal experiments, and the leukemia effect on humans is also prompted by the following facts: early unprotected radiation workers, the incidence of leukemia is 8-9 times higher than the average doctor; ankylosing spondylitis patients treated with radiation, the incidence of leukemia is 10 times higher than the average person, Japan’s Hiroshima and Nagasaki atomic bomb explosion After the atomic bombings of Hiroshima and Nagasaki in Japan, there was a 30-fold difference in the incidence of leukemia between the residents of the areas exposed to radiation and those who were not.
Chemical factors Many chemicals are known to have leukemia-causing effects, such as benzene, which is widely used in industry. Drugs such as anticancer agents (especially alkylating agents), bismorpholine, chloramphenicol, pau d’arco, tranquilizers, solvents and insecticides can induce leukemia.
The spontaneous leukemia of chickens, mice, cats, cattle and gibbons is closely related to the role of viruses, and the corresponding leukemia viruses have been isolated, and it has been proved that these viruses are retroviruses, which are C-shaped under the electron microscope, so they are also called C-type RNA viruses, whose mechanism of causing leukemia is to synthesize DNA through the action of reverse transcriptase and integrate it into the host cell DNA The mechanism of leukemogenesis is the synthesis of DNA by reverse transcriptase and its integration into the host cell DNA, thus altering the biological properties of the host cells and transforming normal stem cells into malignant cell lines. A new strain of virus (HTLV) was isolated from human T-cell leukemia in 1980 and is the same virus as the adult T-lymphocytic leukemia virus (ATLV) discovered in Japan in 1976. This is a new breakthrough in the study of the cause of human leukemia.
The genetic susceptibility of leukemia can be inferred from the following facts: ① in some high-risk families, the chance of developing leukemia between siblings is four times higher than the normal population; ② identical twin children, one person has leukemia and the other has a 25% higher chance of developing leukemia than the normal population; ③ those with special genetic syndromes, the incidence of leukemia is increased, such as congenital stupidity (Down syndrome), Fanconi anemia, hereditary capillary dilated ataxia, etc.
Despite the existence of these possible causative factors, no single factor can yet adequately explain the entire picture; for example, leukemia occurs in only a very small minority of people exposed to radiation. Therefore, it is hypothesized that the occurrence of leukemia is not a single factor, but may be caused by a combination of factors. Patients may have some congenital susceptibility quality, which then triggers the development of leukemia due to the action of external factors.
The pathophysiology of leukemia Leukemia is a stem cell or clonal disease, i.e., a disease caused by the malignant transformation of one stem cell, which is confirmed by the presence of the Ph chromosome in chronic granulocytic leukemia, as the Ph chromosome is seen not only in the granulocyte lineage but also in the red lineage. megakaryocytes and lymphocytes. In addition, women patients heterozygous for glucose 6-phosphate dehydrogenase (G6PD) have leukemic cells with only monotypic enzymes (A or B). All these facts suggest that the leukemic cells originate from a mutated abnormal stem cell.
The leukemic cells proliferated uncontrollably and lost their ability to differentiate and mature. The proportion of S+G2M phase cells in acute leukemia measured by flow cytometry is lower than normal, indicating that their proliferative activity is lower than normal cells, that is, the proliferation cycle of leukemic cells is longer than normal cells (about 65-85 hours compared to 24-32 hours) but the imbalance between proliferation and differentiation process results in a large accumulation of leukemic cells in the bone marrow, increased bone marrow pressure, and the sinusoidal gap barrier may be broken This allows immature cells at all stages to enter the bloodstream. Acute granulocytic leukemia cells have a semi-retention period of 24 hours in the blood, compared to 6-7 hours for normal granulocytes. Leukemia cells do not die in a short period of time when they leave the blood vessels and enter the tissues as normal mature cells do, but maintain the ability to continue to divide and form leukemic cell infiltrates in the organs, causing organ and tissue involvement. The leukemia cells are not killed in the short term like normal mature cells, but maintain the ability to continue to divide and form an infiltration of leukemia cells in the organs, causing various corresponding symptoms and signs of organ and tissue involvement.