What causes leukemia?

The causes of leukemia are not 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 malignant growth event-the formation of mutant transformed cells that are either destroyed or their growth is restrained by the body's defense systems. The second event: the second mutation in the transformed clone of cells, or weakening of the defense systems (can occur both perinatally and postnatally). It is believed that the most likely factor that causes the second event is viral infections. There are known risk factors that increase the likelihood of leukemia: primary and secondary immunodeficiencies, aplastic anemia and myelodysplasia, penetrating radiation, certain chemicals (eg benzene), cytostatic and X-ray therapy for tumors.

The pathogenesis of leukemia. According to the generally accepted clonal theory of leukemia, all leukemia cells are descendants of a single ancestral cell, which ceased its differentiation at one of the early stages of maturation. Leukemia swelling is self-sustaining, depresses normal hematopoiesis, metastasizes, and grows outside the hematopoiesis. Part of the leukemia clone of cells is actively proliferating, "growth fraction", the other - "dormant fraction", consisting of cells in a resting phase. It is emphasized that usually the number of leukemic clone at the time of clinical detection of leukemia is about 10 cells. The minimum time required for the formation of such a number of cells is 1 year, the maximum is 10 years, an average of 3.5 years. Hence it follows that the trigger mechanism of leukemogenesis most likely operated in the perinatal period for a child who contracted acute leukemia.

A characteristic feature of the tumor progression in the bone marrow in acute leukemia is the suppression of normal hematopoiesis, which determines the most typical changes that are detected in the peripheral blood of patients with acute leukemia: anemia + neutropenia + thrombocytopenia. This is due to the fact that most blasts in leukemia have the properties of normal cells - hematopoietic precursors, which can suppress the maturation of normal stem cells. According to modern ideas, at the time of achieving the first clinical remission in a child with acute lymphoblastic leukemia (the absence of physical symptoms of acute leukemia, the normal picture of peripheral blood, the content of blast elements in the myelogram of not more than 5% and lymphocytes no more than 20%), he remains at least 10 -109 leukemic cells, that is, chemotherapy in remission must necessarily be continued (at least 3 years). In addition to bone marrow, leukemia cells are especially frequent (up to 75% of patients) present in the brain and its membranes, and in boys very often in the testes. This dictates the need for targeted therapy specifically for these organs (local X-ray therapy, endolyumbal administration of chemotherapy drugs, etc.).

There are 3 morphological variants of acute lymphoblastic leukemia:

• L1 (mainly small lymphoblasts with homogeneous nuclear chromatin, clearly colored, without nucleoli, with a small amount of cytoplasm);
• L2 (large lymphoblasts, heterogeneous in size, with an irregular nucleus membrane, a clear one or more nucleoli, more cytoplasm);
• L3 (lymphoblasts are large, their size does not vary, the pronounced basophilia of the cytoplasm with its characteristic vacuolization).

Membrane and other marker antigens are isolated:

• T-cell acute lymphoblastic leukemia (15-25% of all ALL in children);
• B-cell and pre-B-cell (1-3% ALL in children);
• O-cell - unidentifiable acute lymphoblastic leukemia (neither on the surface of the lymphoblasts, nor in the cytoplasm, immunoglobulins, CD ⁴ and other markers of T cells) - 70-80% of children with ALL.

Among the OnLL are:

• M1-myeloblast, there is no maturation;
• M2-myeloblast, incomplete maturation;
• M3-promyelocytic;
• M4-myelomonoblast;
• M5 monoblast;
• Mb-erythromyelosis;
• M7-megakaryoblastny.

In chronic myelogenous leukemia, an adult type, a juvenile type, and a blast crisis are identified. Congenital leukemia is usually described as a particular form of acute leukemia.