Classification of acute myeloblastic leukemia

Historically, the diagnosis of acute myeloblastic leukemia is based on cytomorphology. The disease is a morphologically heterogeneous group.

Currently, the classification according to the criteria of the FAB (French-American-British Cooperative Group) is generally accepted . The basis of this classification is the correspondence of the morphological substratum of leukemia to a certain number and the level of differentiation of normal hematopoietic cells.

FAB classification of acute myelogenous leukemia

Notation	Name	Characteristic
AML-M 0	AML with minimal differentiation	Absence of maturation, activity of myeloperoxidase less than 3%, are immunological markers of myeloid differentiation
AML-M 1	AML without maturation	The number of blasts is greater than or equal to 90% of non-erythroid cells, myeloperoxidase activity is less than 3%
AML-M 2	AML with maturation	More than 10% of myeloid cells have signs of maturation to promyelocytes, the number of monocytes is less than 20%
AML-M 3	Acute promyelocytic leukemia	Dominant cells - promyelocytes with pronounced atypia
AML-M 3a	Acute promyelocytic leukemia	The dominant cells are promyelocytes with microglyculation and a sharply positive response to myeloperoxidase
AML-M 4	Acute myelomonocytic leukemia	The number of myelomonocytic power cells with a monocyte component of more than 20% and less than 80%
AML-M 4 E 0	Acute myelomonocytic leukemia	Option M, with atypical eosinophils (> 5%)
AML-M 5a	Acute monoblast leukemia	The number of monoblasts in the bone marrow is> 80%
AML-M 5b	Acute monoblast leukemia	The number of monoblasts and monocytes in the bone marrow of 80%
AML-M 6	Acute erythroid leukemia	The proportion of erythroblasts among the nuclears in the bone marrow is £ 50%, the fraction of blasts among non-erythroid cells is more than 30%
AML-M 7	Acute megakaryocytic leukemia	Morphological features of megacaryoblasts, CD4V, CD6V

Morphological and immunological signs

Morphological finding, highly specific for acute myeloblastic leukemia, is the so-called Auer sticks. If a negative reaction to myeloperoxidase, which is typical for variant M ₀, and exhibit Auer rods, it is necessary to expose the diagnosis of acute leukemia embodiment M ₁. In the variants M ₁ and M ₂ with t (8; 21), we often observe long tender thread-like Aueer sticks; With variant M ₃ in the cytoplasm, one can see the bundles of these rods.

Immunological signs of myeloid differentiation include non-linear markers of hematopoietic precursors CD34 and HLA-DR, panmyeloid markers CD13, CD33 and CD65; markers associated with monocytes and granulocytes CD14 and CD15; linear megakaryocyte markers CD41 and CD61; intracellular myeloperoxidase.

The value of flow cytofluorometry in the diagnosis of acute myeloblastic leukemia is significant in cases when verification of variants M ₀ and M _{1 is} necessary , as well as in the diagnosis of biphenotypic leukemia. In addition, the method makes it possible to distinguish variants of M ₀ and M ₁, as well as variants with granulocyte differentiation - M ₂ and M ₃.

To determine the treatment strategy, it is important to isolate the so-called acute biphenotypic leukemia (biphenotypic acute leukemia, BAL). The criteria for the diagnosis of biphenotypic leukemia are based on the evaluation of the ratio of specific lymphoid and myeloid markers expressed by imperious cells.

Cytogenetic characteristics

The importance of modern laboratory studies in the diagnosis of acute myeloblastic leukemia multiplied over the past two decades. Cytogenetic characteristics became the most important, they were recognized as decisive prognostic factors. Prior to the early 1990s, studies were conducted at the cellular level: the structure and number of chromosomes, the presence of chromosomal aberrations in tumor cells were evaluated. Later, studies were supplemented with molecular biological methods, the subject of study became chimeric genes, which appeared as a result of chromosome aberrations, and proteins - the products of their expression. Cytogenetic changes in leukemic cells are found in 55-78% of adult patients and in 77-85% of children. Below is a description of the most frequent and clinically significant chromosomal aberrations in acute myelogenous leukemia and their prognostic significance.

The most frequent chromosomal aberration is t (8; 21) (q22; q22), identified in 1973. In 90% of cases, t (8; 21) is associated with variant M2 in 10% - with M1. The translocation t (8; 21) is referred to as the "favorable forecast" aberration. It is found in 10-15% of children with acute myeloblastic leukemia.

The translocation associated with acute promyelocytic leukemia is t (15; 17) (q22; ql2) to form the chimeric PML- RARa gene . The frequency of detection of this anomaly is 6-12% of all cases of acute myeloblastic leukemia in children, with the variant M ₃ it is equal to 100%. The PML-RARa transcript is a marker of leukemia, that is, patients who achieve remission are not detected, and its re-identification during morphological remission is a precursor to the clinical recurrence of acute promyelocytic leukemia.

The inversion of chromosome 16-inv (16) (pl3; q22) - and its variant t (16; 16) are characteristic of myelomonocytic leukemia with eosinophilia M ₄ E ₀, although they are also observed in other variants of acute myeloblastic leukemia.

Re-Arrangement 1 Iq23 / MLL. Region 23 of the long arm of the eleventh chromosome quite often becomes a site of structural rearrangements in children with acute leukemia, both lymphoblastic and myeloblastic. In primary acute myeloblastic leukemia, anomaly of llq23 is detected in 6-8% of patients. At secondary - in 85% that is connected with influence of epipodophyllotoxins - topoisomerase inhibitors.

The inversion of inv (3) (q21q26) / t (3; 3) (q21; q26) is described for all variants of acute myelogenous leukemia, with the exception of M ₃ / M _3v and M ₄ E ₀. Despite the absence of a connection between a certain FAB variant and the inversion of chromosome 3, in the majority of patients in the bone marrow there are common morphological signs: an increase in the number of megakaryocytes and numerous micromegacaryocytes.

The translocation t (6; 9) (p23; q34) is described in more than 50 patients with acute myeloblastic leukemia. In most cases this is the only chromosomal abnormality. Somewhat more often t (6; 9) is detected in patients with M ₂ and M ₄ variants, although it occurs in all forms of acute myeloblastic leukemia.

The translocation t (8; 16) (pll; pl3) is described in 30 patients with acute myeloid leukemia, mainly in variants M ₄ and M ₅. More often anomaly is found in young patients, including children under one year old.

Monosomy (-5) and division of del (5) (q-). The loss of the site of the long arm or the entire fifth chromosome is not associated with any particular variant of acute myeloblastic leukemia. This is often an additional anomaly in complex aberrations.

Monosomy (-7) and division of del (7) (q-). Monosomy in the seventh pair of chromosomes is the second in frequency, after trisomy (+8), aberration among quantitative translocations (that is, translocations that change the number of chromosomes).

Trisomy (+8) is the most frequent quantitative aberration, accounting for 5% of all cytogenetic changes in acute myeloblastic leukemia.

Deletion del (9) (q-). The loss of the long arm of the ninth chromosome often accompanies favorable aberrations t (S; 21), less often inv (16) and t (15; 17), without affecting the prognosis.

Trisomy (+11), like other trisomy. May be a solitary anomaly, but is more common with other numerical or structural chromosomal aberrations.

Trisomy (+13) in 25% is a solitary aberration, more often observed in patients aged 60 years. It is associated with a good response to therapy, however, relapses are common and overall survival is low.

Trisomy (+21). This anomaly is found in 5% of patients with acute misloblast leukemia, less than 1% of cases it is solitary. There was no connection with any variant of the FAB.

In addition to the above, there are translocations described in very few patients, whose role in the development of the disease and prognostic significance are not clear. These are quantitative aberrations of the fourth, ninth and twenty-second pairs of chromosomes, as well as structural translocations t (l; 3) (p36; q21). T (l; 22) (pl3; ql3), t (3; 21) (q26; q22), t (7; ll) (pl5; pl5). T (ll; 17) (q23; q25) and t (16; 21) (pll; q22).

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]