What causes leukemia?

The causes of leukemia have not been established. It is believed that oncogenes - cellular genes homologous to retroviruses that cause leukemia in experimental animals and T-cell lymphoma (more often in adults) - are transmitted antenatally and in humans, leading to the first event of malignant growth - the formation of mutant transformed cells that are either destroyed or their growth is restrained by the body's defense systems. The second event: a second mutation in a transformed clone of cells, or a weakening of the defense systems (can occur both perinatally and postnatally). It is believed that the most likely factor causing the second event is viral infections. Risk factors that increase the likelihood of leukemia are known: primary and secondary immunodeficiencies, aplastic anemia and myelodysplasia, penetrating radiation, some chemicals (for example, benzene), cytostatic and X-ray therapy for tumors.

Pathogenesis of leukemia. According to the generally accepted clonal theory of leukemogenesis, all leukem cells are descendants of one parent cell that stopped differentiating at one of the early levels of maturation. A leukem tumor is self-sustaining, inhibits normal hematopoiesis, metastasizes, and grows outside the hematopoietic organs. Part of the leukem cell clone is actively proliferating, the "growth fraction," while the other part is the "dormant fraction," consisting of cells in the resting phase. It is emphasized that the number of a leukem clone at the time of clinical detection of leukemia is usually about 10 cells. The minimum time required for the formation of such a number of cells is 1 year, the maximum is 10 years, with an average of 3.5 years. It follows that the trigger mechanism of leukemogenesis most likely acted on a child who developed acute leukemia in the perinatal period.

The most characteristic feature of tumor progression in the bone marrow in acute leukemia is the suppression of normal hematopoiesis, which determines the most typical changes found in the peripheral blood of patients with acute leukemia: anemia + neutropenia + thrombocytopenia. This occurs due to the fact that most blasts in leukemia have the properties of normal cells - hematopoiesis precursors, which can suppress the maturation of normal stem cells. According to modern concepts, at the time of achieving the first clinical remission in a child with acute lymphoblastic leukemia (absence of physical symptoms of acute leukemia, normal peripheral blood picture, the content of blast elements in the myelogram is no more than 5% and lymphocytes are no more than 20%), he has at least 10 -109 leukemic cells, i.e. chemotherapy in remission must be continued (at least 3 years). In addition to the bone marrow, leukemic cells are especially often (up to 75% of patients) present in the brain and its membranes, and in boys very often in the testicles. This dictates the need for targeted therapy specifically for these organs (local X-ray therapy, endolumbar administration of chemotherapy, etc.).

There are 3 morphological variants of acute lymphoblastic leukemia:

• L1 (lymphoblasts are predominantly small in size with homogeneous nuclear chromatin, clearly stained, without nucleoli, a small amount of cytoplasm);
• L2 (large lymphoblasts, heterogeneous in size, with irregular nuclear membrane, one or more distinct nucleoli, large amount of cytoplasm);
• L3 (lymphoblasts are large, their sizes do not vary, pronounced basophilia of the cytoplasm with characteristic vacuolization).

According to membrane and other marker antigens, the following are distinguished:

• T-cell acute lymphoblastic leukemia (15-25% of all ALL in children);
• B-cell and pre-B-cell (1-3% of ALL in children);
• O-cell - unidentifiable acute lymphoblastic leukemia (no immunoglobulins, CD ⁴ or other T-cell markers were detected on the surface of the lymphoblasts or in the cytoplasm) - 70-80% of children with ALL.

Among ONLLs, the following stand out:

• M1-myeloblastic, no maturation;
• M2-myeloblastic, incomplete maturation;
• M3-promyelocytic;
• M4-myelomonoblastic;
• M5-monoblastic;
• MB-erythromyelosis;
• M7-megakaryoblastic.

Chronic myelogenous leukemia is divided into adult type, juvenile type, and blast crisis. Congenital leukemia is usually described as a special form of acute leukemia.