As MM progressed, there was a deterioration in the indices of cellular and humoral immunity .

The respiratory function was studied by spirography in 70 patients with MM without concomitant COPD. In half of the patients (35 people), no violations of VFL were detected. These are patients from group I and group II, with a disease duration of 1-2 years, in whom no changes were detected during x-ray examination of the lungs. In 35 patients, moderate violations of VFL were diagnosed: in 10 patients in restrictive mode, and in 25 in mixed types. These are patients of group II, who had a diagnosis of MM more than two years ago, and patients from group III. In all, during the X-ray examination of the lungs, changes in the interstitial type were observed (increased vascular pattern, pneumosclerosis and emphysema). According to spirography, 19 patients with myeloma G, 10 with myeloma A,1 with non-secretive myeloma and 5 people with Bens-Jones myeloma, of whom 15 patients had ESRD. Most of these patients were diagnosed with a small reduction in lung volumes. Reduction of VC was diagnosed in all 35 patients (68.4 ± 2.0% D; P <0.001). In 25 patients, a moderate decrease in FEV was observed. 1 (72.9 ± 2.1; P <0.001).

Reduction of VC indicates a loss of elasticity in the lungs and the development of a restrictive respiratory failure (DN). Increased plasma viscosity, the presence of intravascular protein stasis, and increased protein infiltration into the alveoli lead to the lysis of the elastic framework of the lungs. Dystrophy of the elastic framework and the development of emphysema contributes to impaired blood circulation in the lungs in these patients. The filling of part of the alveoli with paraprotein with MM leads to the shutdown of these alveoli from ventilation and the development of emphysema, which in this case is also of compensatory nature. [57]. This reasoning is also supported by a large number of patients with myeloma A, who have impaired VFL, as myeloma A has a more pronounced hyperviscose syndrome . Specific lymphoid and plasma cell lung infiltration may contribute to the development of restrictive type DN. In chronic kidney disease, an important reason for the development of a restrictive type of DN is the presence of uremic changes in the lungs – uremic pulmonary edema, uremic pneumonitis and calcification. A decrease in the FEV 1 value combined with a decrease in the VC indicates the development of a mixed type of DN. When conducting radiological (including ERTG and CT) and bronchoscopic examinations, no patient had an intrabronchial myeloma growth. Therefore, the decrease in FEV 1 can be attributed to edema, specific lymphoid and plasma cell infiltration, sclerotic changes of the bronchial mucosa, with the addition of CRF to uremic lesions, nephrogenic edema and uremic bronchitis. The above changes are more pronounced in the later stages of MM tumor progression. Therefore, it was not revealed in patients with IA, IIA, or the IIA stage of myeloma with a short tumor duration of any violations of VFL recorded by the method of spirography.

The parameters of peak flow measurements of patients with normal spirogram indices did not differ from those in the control group and were within 95% of the proper values ​​in the morning and 100% in the evening, the daily fluctuations averaged up to 5% of the initial value. The PSV data of patients who had a moderate decrease in FEV 1 during spirography were lower than in the control group, averaging 65% D in the morning and 75% D in the evening. Daily changes in HRP throughout the study did not change and were within 10%.

In group I patients, the value of bronchial resistance (R aw ) on inspiration (2.78 ± 0.1 cm water / l / s) and on expiration (3.06 ± 0.08 cm water / l / s) did not significantly differ from similar indicators in the control group (2.8 ± 0.1 and 3.0 ± 0.06 cm. / l / s, respectively; P> 0.05). In group II, the value of bronchial inspiratory resistance (3.1 ± 0.2 cm. Water / l / s) did not change (P> 0.05), R aw during exhalation was increased (3.9 ± 0.2 see / l / s; P <0.001). In patients with group III, a significant increase in bronchial resistance was noted: R aw on inspiration – 4.2 ± 0.15 cm water / l / s and R aw on expiration – 4.5 ± 0.26 cm. water / l / s (P <0.001). In patients of group II, plasma-cell and lymphoid infiltration of the bronchi, edema and sclerosis of the bronchial mucosa are already taking place. The leading cause of a pronounced increase in bronchial resistance in patients with group III is nephro genic edema of the lungs and bronchial mucosa, as a manifestation of renal failure.

Diagnostic fibrobronchoscopy was performed on 60 patients with MM who did not abuse smoking and did not have concomitant COPD (20 patients of group I, 20 patients of group II, and 20 patients of group III). All patients of group I had a bronchoscopic picture of a normal tracheobronchial tree. No hypersensitivity of the bronchi was observed.

In 10 patients of group II, bilateral diffuse atrophic endobronchitis was diagnosed. The bronchial mucosa in these patients was atrophied, pale, thinned. In the lumen of the bronchi mucous secret was absent or was very scarce. A bronchoscopic picture of a normal tracheobronchial tree was diagnosed in 10 patients. In all patients, contact bleeding of the bronchial mucosa was noted.

Bilateral diffuse atrophic endobronchitis was diagnosed in 12 patients of group III. The bronchial mucosa was atrophied, pale, thinned. In 8 patients of this group, there was a picture of a normal tracheobronchial tree. As in patients of group II, in all patients of group III, contact bleeding of the bronchial mucosa was observed, due to impaired hemostasis in the later stages of tumor progression in patients with MM . Thus, when conducting fibrobronchoscopy in 50% of patients with MM IIIA and in 60% of patients with renal insufficiency, bilateral diffuse atrophic endobronchitis occurs (40% of the total number of patients with MM).

In patients with MM of group III, pr and carrying out zonal lung reography , there is a decrease in general and regional ventilation of the lungs. A significant decrease in ventilation in all zones of both lungs and a decrease in the total MOBP from all zones of the lungs by 48.8% (P <0.001) were diagnosed. There is a redistribution of ventilation from the lower and middle to the upper zones of both lungs . A decrease in the pulsatory blood flow in both lungs was diagnosed. The cumulative MPCr index is reduced compared with the control by 46.5% (P <0.001) . In group III, due to uremic damage of the heart and blood vessels, the precapillary vascular resistance reaches maximum values. In patients with renal failure, a significant increase was diagnosed. DSC in the middle and lower zones of both lungs. In group III, the VPO in the right lung had no significant differences compared with the control (p> 0.05). On the left, the overall indicator of HPE was reduced (p <0.05), due to a decrease in the VPO of the lower zone (p <0.001). The HPE of both lungs in group III patients did not have significant differences with the control group (1.1 ± 0.053; p> 0.05).

In patients of group I, the pO2 indicator did not significantly differ from that in the control group. The decrease in pO2 in patients of groups II and III is explained by the progression of regional ventilation disorders as the tumor process develops in patients with MM. The leading role in the disturbance of blood gas composition in MM is associated with a decrease in ventilation and lung perfusion, but the progression of the anemic syndrome as the tumor process develops also plays an important role .

In group I, the SrDLA index (14.67 ± 0.5 mm Hg) did not have significant differences compared with the control group (14.99 ± 0.61 mm Hg; P> 0.05). Patients II (18.7 ± 1.0 mm Hg; P <0.05) and III (22.8 ± 0.5 mm Hg; P <0.001) of the groups showed a significant increase in SrDLA compared to control.

Echocardiography and ICGD were performed on 50 patients with MM aged 33 to 70 years without concomitant COPD (12 patients from I, 27 of II, and 11 of Group III). Patients with diseases accompanied by a primary lesion of the left heart were excluded from the study. Pulmonary hypertension was diagnosed in 26 patients (52%). The SrDLA index in these patients was within 21–39 mm Hg, and averaged 23 ± 0.9 mm Hg. All patients with PH belonged to groups II and III (17 and 9 people, respectively). In patients with renal insufficiency, the highest rates of SrDLA were noted. In 24 patients (48%), the average SrDLA in rest did not exceed 20 mm. Hg Art. Of these, in 17 people it was within 9–16 mm. Hg Art. and in 7 – 17 – 20 mm. Hg Art.

Patients with MM, in whom, according to echocardiographic studies, an increase in SrDLA is diagnosed, these are patients with a pronounced destructive process in the bones, including the ribs, sternum, and thoracic spine. Some of them had significant chest deformity. Violation of the chest excursion (due to the osteodestructive process) is an important reason contributing to the development of hypoxemia and an increase in pressure in the aircraft system. In addition to hypoxemia, endothelial dysfunction and, in the presence of CRF, acidosis contribute to the development of PH in patients with MM without broncho-obstructive syndrome (the pH value of blood in patients of group III was on average 7.24 ± 0.03).

Indicators SrDLA in patients with MM, without broncho-obstructive process.

TMPS PZHD increases in patients of group II and reaches maximum values ​​in group III. The CRV of the pancreas reaches significant differences, compared with the control, only in group III. A study of the functional capacity of the right heart in patients of group I was diagnosed with a significant decrease in the ratio of E / A TK compared with the control, i.e. already in the early stages of the tumor diastolic dysfunction of the pancreas is formed. Patients of group II were diagnosed with a decrease in E TK and an increase in A TK , reducing the ratio of E / A. In group III, more significant impairments of pulmonary hemodynamics were revealed. Marked hypertrophy and dilatation of all cavities of the heart. Reduced ejection fraction of the pancreas. KDO and CSR RV were increased. Increased cardiac index of the pancreas, which is associated with an increase in heart rate in the terminal stage of hemoblastosis due to uremic intoxication and anemia. Revealed a reliable decrease in E TK , an increase in A TK and a decrease in the E / A ratio. Thus, in patients with MM in the presence of CRF, the greatest changes in the systolic and diastolic functions of the pancreas were observed .

TMZS LVZh increased already in patients of group I. In the process of tumor progression, it continues to increase, reaching maximum values ​​in group III. The thickness of the interventricular septum is increased in patients with groups II and III. In group I patients, the E / A MK ratio decreased ; LV diastolic dysfunction has occurred. In the process of tumor progression, the ratio of E / A MK continued to decline. Severe dilatation of the LV was diagnosed only in the presence of CRF (group III). In patients of group III, a significant increase in LV size and their corresponding volumes was observed compared with the control group . In the process of tumor howling progression (II and III group) increased MO LV SI LV after effect of increasing heart rate. LV EF was reduced only in patients with MM in the presence of renal failure .

The revealed changes can be explained by impaired blood rheology due to paraproteinemia, cardiotoxic effects of cytostatics, tumor intoxication, anemia, lymphoid and plasma cell infiltration of the myocardium. But dilatation of the cavities of both ventricles, an increase in their size and corresponding volumes, a decrease in the ejection fraction are diagnosed only in patients with MM with chronic renal failure. Many patients with MM are elderly people, they have coronary heart disease diagnosed , which also contributed to the violation of the LV myocardium trophism and the development of circulatory failure.

Thus, it can be concluded that the development of pulmonary hypertension in MM is promoted by: 1) hypoxemia due to impaired excursion of the chest and diaphragm, severe inflammatory and specific paraproteinemic and uremic processes in the lungs, and impaired blood rheology Ic in the vessels of the ICC, 2) endothelial dysfunction, 3) myocardial degeneration, 4) in the presence of renal failure – acidosis.

Based on the analysis of the data of spirography, peak flow measurements, pneumotachography and ultrasound methods for examining hemodynamics of the ICC, we can conclude:

1. In patients with MM in the late stages of tumor progression, there is a moderate impairment of ventilation function of the lung in restrictive and mixed types. This is due to a decrease in the elastic capacity of the lungs due to plasma hyperviscosity, lung paraproteinosis, impaired blood circulation in the lungs, specific lymphoid and plasma cell infiltration of the lungs and bronchi, in renal insufficiency by the presence of specific uremic lesions — nephrogenic pulmonary edema, uremic pneumonitis, calcification.

2. As MM progresses, bronchial resistance rises, reaching maximum values ​​in patients with renal insufficiency.

3. In the process of tumor progression in MM, there is a decrease in the parameters of endobronchial microhemocirculation. The leading causes of impaired microhemocirculation in patients with MM are syndrome of increased blood viscosity and renal insufficiency.

4. In patients with MM at the late stages of tumor progression, dysfunction of the vascular endothelium of the microvasculature was diagnosed.

5. Violation of microhemocirculation in patients with MM caused by atrophic changes of the bronchial mucosa. In 40% of these patients, fibrobronchoscopy was diagnosed with bilateral diffuse atrophic bronchitis.

6. After reaching the phase of a stable plateau, the main indicators of the endobronchial LDF are improved, but not fully normalized due to the multifactor nature of the microcirculatory disorders.

7. In the process of development of MM, disorders of general and regional ventilation of the lungs and pulmonary blood flow are progressing, which is characterized by a decrease in ventilation and perfusion indices each zone separately and in general for both lungs. There is a redistribution of ventilation and blood flow from the lower and middle zones to the upper zones of both lungs. These changes are due to the progression of specific myelomatous lesions of the bronchopulmonary system and the diaphragm.

8. In patients with MM with a pronounced osteo-destructive process of the chest, a significant decrease in the excursion of the diaphragm was observed with calm and forced respiration.

9. In patients with MM in the process of tumor progression, the development of pulmonary hypertension is noted. The development of pulmonary hypotension in MM is promoted by: a) hypoxemia due to impaired excursion of the chest and diaphragm, the presence of specific myelomatosis and uremic processes in the lungs, impaired microcirculation and rheology of blood in the ICC vessels, b) endothelial dysfunction, c) myocardial dystrophy, d) acidosis in the presence of renal failure.

10. With the progression of the tumor process there is a violation of the hemodynamics of the ICC. In patients with renal insufficiency, a significant impairment of the systolic and diastolic functions of the right and left ventricles was revealed.

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.