Acute myeloblastic leukemia (M0, M1, M2). The term “acute myeloblastic leukemia” unites three disease subtypes, which differ in the degree of differentiation and maturity of leukemic cells — myeloblasts. In the FAB classification, these variants are designated by numbers: M0 is undifferentiated AML, M1 is acute myeloid leukemia without maturation, M2 is acute myeloid leukemia with maturation.
Acute myeloblastic leukemia with minimal differentiation (M0) is approximately 5% of all acute non-lymphoblastic leukemias. As mentioned, this diagnosis can only be made by performing immunophenotyping, since, in cytochemical analysis, cells cannot be assigned to any subtype. Fundamental is the detection of myeloperoxidase enzyme using monoclonal antibodies in flow cytofluorometry.
Cells with M0 also express the following myeloid antigens: CD13, CD33, CD34. For this form of leukemia, characteristic chromosomal aberrations associated only with this subtype of acute myeloid leukemia were not found. The prognosis for standard treatment is unfavorable.
Acute myeloblastic leukemia without signs of cell maturation (Ml) is 15% of all AML. In this form of AML, a minimal degree of myeloid differentiation is determined, i.e., less than 3% of promyelocytes are detected in bone marrow punctate, Auer sticks are absent. Cytochemically myeloperoxidase is determined in a small percentage of blast cells. Typical immunophenotypic markers are CD13, 14, 15, 33, 34, HLA-DR.
Somewhat more often than with other morphological forms of AML, there is an inversion of chromosome 3 – inv (3), which is associated with thrombocytosis in the debut of the disease; in 3% of cases, when M1, t (9; 22) is detected.
Acute myeloblastic leukemia with signs of maturation (M2) makes up about 25% of all acute myeloid leukemias. Typical immunophenotypic markers are CD13, 15, 33, 34, HLA-DR. In 1/3 of all cases of M2, t (8; 21) is defined. This translocation occurs, although very rarely, with myelomonoblastic acute leukemia. For myeloblastic leukemias, an increase in the size of organs, extramedullary lesions, are not typical.
In acute myeloid leukemia with t (8; 21), splenomegaly is found in 25% of patients, chloromas in 20%, eosinophilia, morphological signs of abnormal maturation of neutrophils (hypogranularity, pseudo-Selger anomaly) are described. There are cases of detection of a small number of blast cells in bone marrow punctate (less than 20%) at the time of diagnosis of acute myeloid leukemia with t (8; 21). With a small number of blast cells, patients with t (8; 21) still make a diagnosis of acute leukemia, and not MDS.
As noted, this group of acute myeloid leukemia is currently regarded as a separate leukemic clinicopathologic syndrome; in the modern classification, it is distinguished within a separate category – acute myeloid leukemia with certain chromosomal aberrations. As a result of this translocation, the AML1 gene located on the long arm of chromosome 21 and encoding the transcriptional regulatory factor CBFa is transferred into the region of the gene encoding ETO protein located on the long arm of chromosome 8.
The result of translocation is the chimeric AML1-ETO gene and, accordingly, the CBFa-ETO protein. Normally, CBFa protein binds directly to a DNA molecule, and CBFp protein is attached to it, increasing the affinity of CBFa to DNA. As a result of the formation of this protein complex, transcription of the genes of proteins responsible for myeloid differentiation is activated (IL-3, GM-CSF, myeloperoxidase). The chimeric protein does not lose the ability to bind to DNA, however, as a result of its action, transcription inhibition occurs and, accordingly, the mechanisms of myeloid cell differentiation are violated.
Acute myeloblastic leukemia with t (8; 21) has a good response to chemotherapy and good long-term results. Cells of this variant of acute myeloid leukemia are very sensitive to the effects of cytosine arabinoside, especially in high dosages. In this regard, when using this variant of acute myeloid leukemia in three or more courses of this drug in a dose of 3 g / m2 for 3 days, the probability of disease-free survival of patients increases to 70%.
In this form of acute myeloid leukemia, a unique persistence phenomenon has been described during the period of complete clinical and hematological remission of the minimal residual population of leukemic cells. This is determined by PCR, which allows detection of 1 cell carrying the indicated translocation among 104-5 normal ones. In patients who completed treatment and are in complete remission for a long time (up to 8 years), the product of the chimeric CBFa-ETO gene is detected by PCR due to t (8; 21).
This fact suggests that this translocation, although it is a marker of the disease, does not constitute the final stage of leukemogenesis, and additional effects are required to transform this clone into a truly leukemic one.
Among acute myeloblastic leukemias with differentiation (M2), another subtype is distinguished with a characteristic cytogenetic anomaly and clinical and laboratory signs — acute myeloblastic leukemia with basophilia and t (6; 9). The prognosis for this form of leukemia is extremely unfavorable. Basophilia is rarely found in M4 variants.