Classification of acute myeloblastic leukemia

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

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

FAB classification of acute myeloid leukemia

Designation	Name	Characteristic
AML-M 0	AML with minimal differentiation	No maturation, myeloperoxidase activity less than 3%, there are immunological markers of myeloid differentiation
AML-M 1	AML without maturation	Blast count 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 show signs of maturation to promyelocytes, the number of monocytes is less than 20%
AML- M3	Acute promyelocytic leukemia	Dominant cells are promyelocytes with pronounced atypia
AML-M 3a	Acute promyelocytic leukemia	The dominant cells are promyelocytes with microgranulation and a sharply positive reaction to myeloperoxidase.
AML- M4	Acute myelomonocytic leukemia	The number of myelomonocytic cells with a monocytic 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 monoblastic leukemia	The number of monoblasts in the bone marrow is >80%
AML-M 5b	Acute monoblastic leukemia	The number of monoblasts and monocytes in the bone marrow is 80%
AML-M 6	Acute erythroid leukemia	The proportion of erythroblasts among nuclear cells in the bone marrow is £50%, the proportion of blasts among non-erythroid cells is more than 30%.
AML-M 7	Acute megakaryocytic leukemia	Morphological features of megakaryoblasts, CD4V, CD6V

Morphological and immunological features

A morphological finding that is highly specific for acute myeloblastic leukemia is the so-called Auer rods. If the myeloperoxidase reaction is negative, which is typical for the M _{0 variant, and Auer rods are detected, a diagnosis of acute leukemia of the M1} variant must be made. In the M ₁ and M ₂ variants with t(8;21), long, delicate, thread-like Auer rods are often observed; in the M ₃ variant, bundles of these rods can be seen in the cytoplasm.

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

The importance of flow cytofluorometry in the diagnosis of acute myeloblastic leukemia is significant in cases where verification of variants M ₀ and M ₁ is necessary, as well as in the diagnosis of biphenotypic leukemia. In addition, the method allows one to differentiate between variants M ₀ and M ₁, as well as variants with granulocytic differentiation - M ₂ and M ₃.

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

Cytogenetic characteristics

The importance of modern laboratory tests in the diagnosis of acute myeloid leukemia has increased many times over the past two decades. Cytogenetic characteristics have acquired the greatest importance; they are recognized as decisive prognostic factors. Until 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 assessed. Later, molecular biological methods were added to the studies; the objects of study were chimeric genes that appeared as a result of chromosomal aberrations, and proteins - products of their expression. Cytogenetic changes in leukemic cells are detected in 55-78% of adult patients and in 77-85% of children. Below is a description of the most common and clinically significant chromosomal aberrations in acute myeloid leukemia and their prognostic significance.

The most common chromosomal aberration is t(8;21)(q22;q22), identified in 1973. In 90% of cases, t(8;21) is associated with the M2 variant, in 10% - with M1. Translocation t(8;21) is considered a "favorable prognosis" aberration. It is found in 10-15% of children with acute myeloid leukemia.

Translocation associated with acute promyelocytic leukemia - t(15;17)(q22;ql2) with formation of chimeric gene PML-RARa. The frequency of detection of this anomaly is 6-12% of all cases of acute myeloblastic leukemia in children, with the M ₃ variant it is 100%. The PML-RARa transcript is a marker of leukemia, i.e. it is not detected in patients who have achieved remission, and its repeated detection during morphological remission is a harbinger of clinical relapse of acute promyelocytic leukemia.

Inversion of chromosome 16 - inv(16)(pl3;q22) - and its variant t (16;16) are characteristic of myelomonocytic leukemia with eosinophilia M4E0 _, although they are also observed in other variants of acute myeloblastic leukemia _.

Rearrangement 1 Iq23/MLL. Region 23 of the long arm of chromosome 11 is quite often the site of structural rearrangements in children with acute leukemia - both lymphoblastic and myeloblastic. In primary acute myeloblastic leukemia, the llq23 anomaly is found in 6-8% of patients. In secondary - in 85%, which is associated with the effect of epipodophyllotoxins - topoisomerase inhibitors.

The inversion inv(3)(q21q26)/t(3;3)(q21;q26) has been described in all variants of acute myeloid leukemia except M3 _/ M3v _and M4E0 _{. Despite the lack of association between a specific FAB variantand} chromosome 3 inversion, most patients show common morphological features in the bone marrow: an increase in the number of megakaryocytes and numerous micromegakaryocytes.

Translocation t(6;9)(p23;q34) has been described in more than 50 patients with acute myeloid leukemia. In most cases, it 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 myeloid leukemia.

Translocation t(8;16)(pll;pl3) has been described in 30 patients with acute myeloid leukemia, mainly with variants M4 _and M5 _. The anomaly is most often detected in young patients, including children under one year of age.

Monosomy (-5) and del(5)(q-) deletions. Loss of part of the long arm or all of chromosome 5 is not associated with any particular variant of acute myeloid leukemia. It is often an additional abnormality in complex aberrations.

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

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

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

Trisomy (+11), like other trisomies, can be a solitary anomaly, but more often occurs in association with other numerical or structural chromosomal aberrations.

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

Trisomy (+21). This anomaly is found in 5% of patients with acute myeloblastic leukemia, in less than 1% of cases it is solitary. No association with any FAB variant has been found.

In addition to those listed above, there are translocations described in a very small number of patients, the role of which in the development of the disease and prognostic significance are unclear. 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).

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