The PML gene is considered a growth regulator gene and plays a role in the maturation and activation of various cells. The product of this gene is a tumor suppressive protein, which is involved in the processes of cell differentiation and suppression of their proliferation, in a number of immunological processes associated, in particular, with the mechanisms of action of IFN-a. Thus, PML protein has been shown to stimulate the expression of class I antigens of the main histocompatibility complex and proteins involved in the movement of peptides to the cell surface in association with class I antigens. A number of studies have demonstrated that PML protein can induce an apoptosis process, both associated and not associated with a caspase mechanism. The PML protein is expressed mainly in differentiated cells in the postmitotic period.

The largest expression of this protein is found in endothelial cells, epithelial cells and macrophages. The PML protein is localized in the cell nucleus in the so-called nuclear bodies (nuclear bodies – NB) or PML-oncogenic domains (POD). These structures were described about 35 years ago, their presence is directly proportional to the level of protein synthesis and inversely proportional to the degree of cell differentiation. NBs are associated with the nuclear matrix, which plays a role in the movement of molecules and the organization of chromatin inside the nucleus. In acute promyelocytic leukemia with t (15; 17), PML protein moves from the NB and is visualized as fine material. After treatment with all-trans retinoic acid, PML is again localized in nuclear bodies. The researchers noted that an increase in the amount of PML protein in cells of the culture of acute promyelocytic leukemia (NB4-line) significantly suppresses its clonogenic activity and malignancy when conducting experiments on nude mice. This allowed the authors to suggest antagonism between the action of PML protein and the protein product of the chimeric PML-RARa gene.

The product of the chimeric PML-RARa gene is a pathological protein that retains the active functional domains of both the RARa protein and PML protein. In ALP, PML-RARa protein accumulates in the cytoplasm and nucleus of myeloid cells in a significantly larger number than normal RARa protein accumulates. The aberrant retinoid PML-RARa receptor with impaired DNA binding activity can attach to DNA in retinoic acid binding regions (RARE) as a homodimer, competing with normal RARa, which can bind to DNA, as indicated, only after heterodimerization with RXR.

It has also been proven that chimeric protein binds actively to RXR, displacing the normal RARa receptor. In the absence of retinoic acid, the chimeric receptor PML-RARa proves to be a stronger transcriptional repressor than the normal receptor.

This is explained by the fact that, forming a repressor protein complex, it is stronger than normal RARa and binds to the corepressor molecules N.COR and SMRT. These corepressor molecules, in turn, are associated with histoacetylases, which change the conformation of the DNA molecule and make it inaccessible for transcription factors. As a result, gene transcription is stopped. In order to cause dissociation of the RARa-corepressor-histone deacetylase complex, the ATRA concentration should be 10-6 mol / l. This significantly exceeds the physiological concentration of retinoic acid (10-9 mol / l), which is required for the dissociation of the complex, which includes the normal RARa receptor. Normally, after binding the ligand (ATRA) to the ligand-binding domain of RARa, corepressors detach (dissociation of the RARa-corepressor-histone deacetylase complex), the RARa receptor configuration changes, resulting in association domains with the TIF1 / TIF2 / CBP transcription coactivators. When APL under conditions of low physiological concentration of retinoic acid, the chimeric PML-RARa protein retains the corepressor deacetylase complex, which slows down the activation process of transcription and blocks the transcription of myeloid differentiation genes.

This block of differentiation can only be removed with a high concentration of retinoic acid, which is achieved during therapy with all-trans retinoic acid (ATRA). The effects of PML-RARa protein are associated not only with the differentiation unit, but also with the regulation of apoptosis and cell growth. Thus, in vitro, cells expressing this protein do not undergo apoptosis in situations where the factors necessary to maintain their viability are removed (serum or granulocyte-macrophage colony-stimulating factor — G-CSF), whereas in the control (if there is no expression of PML-RARa) cells die. From this it follows that this protein maintains the viability of tumor cells by blocking the mechanisms of apoptosis.

As noted, t (15; 17) (q22; ql2-21) is characteristic of acute promyelocytic leukemia. As a result of this translocation, the so-called PML gene (gene of promyelocytic leukemia), located on chromosome 15, is transferred to the long arm of chromosome 17 in the region where the a-receptor retinoic acid (RARa) gene is located.

The RARa gene (retinoic acid receptor a) belongs to a family of receptor genes (genes for steroid hormone receptors, estrogens, thyroid, vitamin D3), which are transcription factors that, in the presence of certain ligands, can either activate or suppress the transactivation of the necessary genes. The ligand for the RARa gene is retinoic acid. Normally, this gene is involved in the regulation of the differentiation of myeloid cells.

It has long been noted that retinoids play a key role in myeloid differentiation, since in vitamin A deficiency, both in humans and experimental animals, there are impaired hematopoiesis, and the administration of retinoids mainly stimulates granulocytopoiesis. Retinoids (all-trans-retinoic acid, 13-cis-retinoic acid, 9-cis-retinoic acid, etc.) are ligands of the nuclear receptor RARa, which is attached to DNA in regions of the binding of retinoic acid (RARE) only after heterodimerization with another retino receptor X (RXR).

In the absence of ligands (retinoids), the heterodimer binds to the corepressors SMRT and N.COR, which in turn are associated with the histone deacetylase-Sin3A complex, which leads to repression of the transcription of the required genes. Histone deacetylases inhibit the transcription mechanisms by attaching the DNA molecule to histones (compact DNA on histones). When retinoic acid binds to RARa, corepressors are exchanged for transcription coactivators, which are associated with histone acetylases, which leads to DNA detachment from histones and activation of the transcription of the necessary genes.

The genes regulated by RARa include genes of cell cycle regulators (cyclins, cyclin-dependent kinases), adhesion molecules (CD11b, CD18), interleukins, monocytic chemoattractant, colony-stimulating factors (G-CSF, IL-1, IL-8), colony-stimulating factors (monocytic CSF and G-CSF receptors), regulators of apoptosis and terminal cell division (transglutaminase II, bc12), coagulation factors (thrombomodulin, tissue factor, urokinase, tissue plasminogen activator, and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors); e RAR).

The incidence of acute promyelocytic leukemia in patients from Latin America is higher than in other ethnic groups – 24.3%, but the clinical features of the disease or any fundamental biological differences are not found in them. S. Santillana et al. a higher detection rate (74.4%) in these patients is one (bcr1) of three transcripts resulting from t (15; 17) than among patients in Italy (59.4%), Spain (56%), UK (61%), China (69%), USA (54%).

The development of acute promyelocytic leukemia as a secondary leukemia associated with prior chemotherapy and radiation has been described. By 1999, about 60 such cases are known, and in most patients this is the second tumor after treatment for cancer of the breast, uterus, and hepatocellular carcinoma.

In 6 out of 60 patients, acute promyelocytic leukemia occurred during the therapy of various types of lymphomas. Patients were treated with drugs such as etoposide, novantron, adriamycin, cyclophosphamide. In 2000, French researchers conducted a retrospective analysis of the diagnosis of acute promyelocytic leukemia at the University Hospital Lille. From 1984 to 2000, 75 patients were diagnosed with ALI, and in nine (12%) of them, the development of ALI was preceded by chemoradiotherapy for breast cancer (n = 4), lung cancer (n = 1), lymphomas (muco-associated – 1, large cell – 3).

The average time from the completion of therapy for the primary tumor to the time of diagnosis of secondary AFL was 24 months (15 months – 8 years). The authors noted an interesting pattern of increasing the frequency of occurrence of secondary APL and shortening the interval before its diagnosis as the aggressiveness of modern therapy increases, especially lymphomas. All secondary OPL were classified as a classic hypergranular variant, in all cases t (15; 17) was detected, the results of treatment for them do not differ from those of primary PLA.

Promyelocytic blast crises of chronic myeloid leukemia (CML) are described. Promyelocytic blast crisis was diagnosed in patients with previously proven chronic myeloid leukemia. In one case, the diagnosis of a promyelocytic crisis was confirmed morphologically, immunophenotypically, and cytogenetically [FISH study for the presence of t (15; 17)]. In another case, a blistering crisis revealed a typical marker of APL – PML-RARa transcript, the crisis developed 4 years after the diagnosis of CML, which was characterized by typical t (9; 22) and coexpression of p190 (e3a2) and p210 (b3a2).

The first works on the cytochemical characterization of blast cells in acute leukemia appeared in the early 60s. During this period, researchers discovered the possibility of differentiating blast elements in acute leukemia, not only by their morphological, but also by physiological (cytochemistry) features.

The classic cytochemical sign of tumor cells in acute promyelocytic leukemia is a very vivid reaction to myeloperoxidase (MPO), Sudan Black (SBB), and chloroacetate esterase. The first in our country and a very detailed description of these signs is given by A. I. Vorobiev et al. in 1968, the authors presented the results of a cytochemical study of blast cells in 11 patients with acute promyelocytic leukemia.

Tumor cells in acute promyelocytic leukemia (APL) have a fairly characteristic immunophenotype. The expression of CD13 and CD33 antigens and a positive reaction with antibodies to myeloperoxidase are determined. The markers of the early stages of differentiation of granulocyte germ cells CD34 and HLA-DR, which are expressed on blast cells in other AML variants, are usually not detected in acute promyelocytic leukemia.

Almost always, with acute promyelocytic leukemia (APL), a reaction with antibodies to the CD9 antigen is positive, and for other forms this marker is not detected. Unfortunately, these antibodies are rarely included in the diagnostic panel.

Rarely, but sometimes, the expression of monocytoid markers CD11b and CD14 is determined, and no correlation with cytochemical reactions to the monocytoid line (nonspecific esterase) is detected. Also, other monocytoid differentiation markers can sometimes be found, such as CD64, very rarely CD65 or CD117. The CD11a antigen, which is expressed on almost all AML cells, is not detected in ALI.

Studies have been conducted to study the expression of lymphoid markers CD7 and CD2. It turned out that the CD7 antigen is always negative, and the CD2 antigen is in some cases positive. Moreover, some researchers propose to allocate as a separate form that variant of APL, which reveals the expression of CD2. Interestingly, there is an association in expression between CD2 and CD34.

Thus, Italian scientists in the analysis of the immunophenotype of blast cells in 114 patients with PLA identified two groups of patients: both CD34 and CD2 (n = 66) are determined on the blast cells, or expression is not determined (n = 20). Positive expression for CD34 was considered the detection of more than 10% of cells expressing CD34, for CD2 – more than 20%. In 28 patients, heterogeneous expression of these antigens was determined.

When comparing clinical, laboratory, cytogenetic data with the indicated immunophenotype, clear correlations were found. With the positive expression of CD2 and CD34, the number of leukocytes in the opening was higher (11.8 • 109 / l versus 1.8 • 109 / l), the number of platelets is smaller (19.5 • 109 / l and 27.5 • 109 / l, respectively ), the percentage of blast cells in the blood was higher (88 and 18%), the bcr3-type of the PML-RAR transcript was determined more often.

Characteristic was the fact that the significance of the differences remained in these parameters and with the exclusion of the micro-granular variant of the APL. So far, no results have been obtained on the effectiveness of modern therapy for the described immunophenotypic variant of APL, therefore it is difficult to interpret the prognostic significance of this phenomenon.

Several groups of researchers have identified significant differences in survival and the likelihood of recurrence in patients with ALI, if CD56 expression is determined on blast cells. The results of the study of Italian scientists GIMEMA patients with PLD clearly show that the expression of CD56 is a negative prognostic sign. Expression is considered positive if 20% or more of the blast cells express the indicated antigen.

Of 100 patients, 15% identified this marker. No differences were found either by sex, age, or the number of leukocytes and platelets in the debut of the disease, nor by the ICE clinic, hemoglobin and fibrinogen content. The duration of remission and the overall survival of these patients was significantly lower than those for whom no expression of CD56 was detected. Other authors confirm this information: if there is CD56 expression, relapse develops in 71.4% of patients, if not, in 12%, which affects the overall survival and the median duration of remission, respectively. Interestingly, these differences are obtained only for APL or AML with t (8; 21), and with other AML variants they are not detected.

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.

The likelihood of the emergence and development of resistance in acute myeloid leukemia is most often associated with increased expression of the multidrug resistance gene and, accordingly, beta-glycoprotein.

The prognosis in patients in whom a large amount of beta-glycoprotein is detected on the cells in the onset of the disease or an increased expression of the MDR1 gene is detected is significantly worse.

No clinical study is currently being conducted without an assessment of cytogenetic markers of leukemic cells. Depending on the long-term indicators in patients with various chromosomal abnormalities, three groups of “cytogenetic” prognosis were identified: favorable, moderate, poor. The criteria for assigning chromosomal abnormalities to a particular risk group vary from one clinical study to another.

These discrepancies relate to a number of aberrations, such as inv16, t (10; 11), 7q-, +8, which are often determined in patients with acute myeloid leukemia and a number of researchers are used as criteria for the differentiated treatment of acute myeloid leukemia.

As can be seen from the table, the number of research groups corresponds to the number of definitions given to groups of prognosis depending on the karyotype anomalies. This may be due both to differences in therapy (although it was very intensive in these studies) and to a small number of patients with each specific chromosomal aberration.

The long-term results in the respective forecast groups, despite the differences, largely coincide. This coincidence is explained by the fact that a small number of patients with a particular chromosomal aberration, analyzed in any prognosis group, cannot fundamentally affect the overall results of treatment.

It should be emphasized that the importance of cytogenetic markers in assessing the prognosis of the disease in a patient with acute myeloid leukemia is lost over time.

The universal prognostic factors in acute myeloid leukemia, as, however, in acute lymphoblastic leukemia and other tumors, is the treatment itself. Therapy should be adequate for doses of cytotoxic drugs, their combination, intervals and duration of treatment.

Inadequate chemotherapy is the only risk factor that is not associated with the biological characteristics of acute leukemia and patient status, and which, unfortunately, does not give chances for long-term survival to the majority of patients. It must be emphasized that the effects of inadequate therapy at the onset of the disease can never be corrected by further treatment, no matter how intense it is, because, as already discussed, the success of chemotherapy is determined by the intensity of the effect on the leukemic clone during the first stages of treatment.

The risk factors, which can also be called universal, include the patient’s age (especially over 60 years), the number of leukocytes in the onset of the disease (more than 30 • 109 / l), high levels of LDH in blood serum (more than 700 units), the period of previous myelodysplasia . Less common and not confirmed by all researchers are the signs by which the prognosis is assessed as follows: the presence of an infection before the start of chemotherapy, high serum creatinine or urine, severe hemorrhagic syndrome in the debut, neuroleukemia.

The morphological variant of acute myeloid leukemia is, of course, a fairly simple sign that allows an approximate assessment of the prognosis of a particular patient. Monoblastic, erythroblastic, megakaryoblastic, acute leukemias are quite unanimously classified as an unfavorable prognosis.

Standard induction chemotherapy is a classifying factor. After completing two courses of induction, patients are naturally divided into two groups: patients in complete remission and with a resistant form of acute myeloid leukemia. All patients with a resistant form of acute myeloid leukemia are in the group of poor prognosis.

The immunological phenotype of blast cells in myeloid leukemia is very diverse, and most often (in 80% of patients) aberrant expression of antigens is determined.

In other words, typical myeloid markers (CD11, CD13, CD14, CD15, CD33, CD36, CD41, CD42, CD65, HLA-DR; antigen of early CD34 precursor cells) can be expressed, first, together with antigens characteristic of lymphoid cells; secondly, their expression may be abnormal in the combination of early and late markers of cell differentiation; thirdly, over-expression of an antigen (for example, CD34) may be observed; fourth, there may be no expression of any antigen (for example, CD13 is expressed, but no CD33 is expressed). It is the aberrant immunophenotype that serves as a marker when monitoring minimal residual disease during remission.

In other cases, the detection of certain antigens on leukemic cells indicates only the aberrant immunophenotype and in some cases correlates with the prognosis.

For example, in acute myeloid leukemia, lymphoid markers occur in 14–60% of patients. According to German researchers, the CD2 antigen was expressed on blast cells in 57% of patients, CD5-y 60%, CD7-y 37%.

A study of the American group CALGB by definition of an immunophenotype in 339 patients with acute myeloid leukemia revealed the following frequency of lymphoid markers: CD2 (T-cell marker) was detected in 21% of cases (45 of 211 patients), CD19 (B-cell marker) – in 14 % (in 41 of 298 patients), CD2 and CD19, studied in combination, in 33% of cases (in 56 of 170 patients). Interestingly, with promyelocytic leukemia, a combination with lymphoid markers is noted 2 times more often, and with myelomonoblastic leukemia with eosinophilia (M4eo), 8 times more often than with other myeloid leukemias.

It is known that both M3 and M4eo are the most favorable variants of acute myeloid leukemia according to the effectiveness of treatment, therefore it is not surprising that in patients whose leukemic cells express, along with myeloid, lymphoid markers, the percentage of remissions was significantly higher (75 vs. 59%; р = 0.04) and overall survival over 2 years is better (43.8 ± 6.3% versus 29.8 ± 3.8%; p = 0.02). Detection of the early antigen of hematopoietic cells CD34 is also of prognostic significance: the prognosis in patients whose cells carry this marker is significantly worse than in those without it. It should be noted that this marker is most often determined in elderly patients with acute myeloid leukemia.

It is assumed that non-random acquired chromosomal aberrations exist in all patients with acute non-lymphoblastic leukemia (ONLL), but are determined using various methods in 70-80%. Detection of karyotype abnormalities allows us to predict the course of the disease and track the minimal residual population of leukemic cells.

Certain associations between cytogenetic and clinico-morphological features have been discussed previously. Fundamentally, at present, cytogenetic markers are becoming decisive in the choice of therapeutic approaches that were previously absolutely standard for all AML variants.

The most frequently detected cytogenetic abnormalities in acute myeloid leukemia include trisomy of chromosome 8, t (15; 17), t (8; 21), inv16, del 5q, 7q, monosomy of chromosome 5 and 7, translocation involving the region 11q23. As previously noted, leukemias with t (15; 17), t (8; 21), invl6 and 11q23 anomaly are classified in a modern category in a separate category. It should be emphasized that if the number of blast cells is less than 20%, but t (15; 17), inv16, t (8; 21) are detected, then the diagnosis of AML is nonetheless established.

Many cytogenetic aberrations, as a result of which one or another chimeric gene appears, can serve as a marker of a tumor clone in the period of clinical and hematological remission, i.e., used to monitor minimal residual disease. The table presents the most widely used in clinical practice molecular markers and the frequency of their occurrence in ONLL.

Unfortunately, when performing reverse transcriptase and direct polymerase chain reactions to determine the minimum residual population of leukemic cells, there are both false positive and false negative results.

The most common cause of false-positive results is not sufficiently accurate execution of the reaction, not in perfectly clean conditions, but false negative – in cases where transcription of mRNA is not detected in clonogenic leukemic cells with a certain chromosomal translocation.

The initial CNS lesion in acute myeloid leukemia is rare and is also most often associated with myelomonoblastic and monoblastic AML variants and during hyperleukocytosis.

In the debut of the disease in the blood are determined by very diverse changes. Power cells are found in 85-90% of patients, and their percentage ranges from 2-3 to 90-95. Neutropenia, anemia, and thrombocytopenia of varying severity are common at the time of diagnosis. In more than half of the patients, the number of leukocytes is increased, but the number of leukocytes more than 100 • 109 / l is determined in less than 20% of patients.

Hyperleukocytosis in acute myeloid leukemia, in contrast to ALL, often has clinical manifestations: leukostasis occurs in brain vessels, causing neurological symptoms (headache, workload, inability to concentrate), in vessels of the lungs, which manifests as respiratory failure, in kidney vessels, etc. e. As a prognostic criterion, the most frequently used leukocyte count is 30 • 109 / l; if at the time of diagnosis their content is more, patients are considered to be at high risk.

In certain forms of acute myeloid leukemia, most often in acute promyelocytic leukemia, a prominent clinical sign is DIC and activated fibrinolysis syndrome, which are manifested by severe bleeding or, less commonly, thrombotic complications. This is due to the release of procoagulants from azurophilic granules of leukemic cells and is often aggravated during cytostatic therapy due to their destruction.

In half of the patients with acute myeloid leukemia, hyperuricemia is observed, especially during the beginning of chemotherapy and tumor cell lysis. With monoblastic and myelomonoblastic acute leukemia, serum levels of lysozyme are possible. The increased content of lysozyme aggravates damage to the renal tubules, causes deep hypokalemia, not associated with diuretics and antibiotics. In a number of patients, an increase in the serum LDH content is noted. This indicator serves as a prognostic criterion: its 2-fold increase in relation to the norm indicates an unfavorable prognosis.

In the bone marrow is found from 20 to 99% of blast cells. The bone marrow is in most cases hypercellular, adipose tissue is completely replaced by tumor cells, the number of megakaryocytes is usually reduced, they are dystrophic. As noted, in 30% of patients with primary AML, one or other signs of hematopoiesis are noted. In this regard, it is unclear why in the modern classification of leukemias with this characteristic, belonging to different morphological and cytochemical variants, belong to a separate category.

Both dizeritroez, and / or dysgranulocytopoiesis, and / or dizegakaryocytopoiesis, or combinations thereof are detected. Dyserythropoiesis is characterized by hyperplasia of the red sprout or its substantial decrease, a disproportionate increase in the number of immature forms, megaloblastoidity, nuclear splitting, multi-core, vacuolization and cytoplasmic outgrowths, ring sideroblasts. Dizgranomonocytopoez is characterized by hyper- or hypoplasia of the cells of the man-made creatures, monitored by the pseudo-Egerger, the pseudopergerian anomaly, the dissociation between the degree of maturity of the nucleus and the cytoplasm, the hypersegmentation of the nucleus, the ring nuclei, microflora of the granulocyte, myelocyte, and the cell culture, the hypersegmentation of the nucleus, the ring nuclei, the microform of the granulocyte, the myelocyte, and the cell culture;

Dimegakaryocytopoiesis includes the following features: hyper- or hypoplasia of the germ, an increase in the number of microforms, single-binuclear megakaryocytes, vacuolization of the cytoplasm.

Trilinear dysplasia occurs on average in 5–7% of patients (with age, the probability of detecting this morphological phenomenon increases by 2–3 times). It was believed that patients in whom, at the time of diagnosis of OL, three-linear hemopoiesis dysplasia is determined, regardless of the ONLL variant, should be included in the group of poor prognosis for long-term survival. However, as emphasized, modern works refute this position.

The diagnostic signs and features of acute myeloid leukemia considered are the result of routine research. No less significant at present for the differential diagnosis and assessment of prognostic factors are those signs that are established during immunophenotyping of power cells, with their cytogenetic and molecular-biological studies.
Source: MedUniver