ANEMIA. LEUКЕМІА Professor Yu.I. Bondarenko

Definition of concept, hematological indexes The anemia is decrease of erythrocytes amount and hemoglobin maintenances in unit of blood volume which is accompanied by qualitative changes of erythrocytes. The quantitative manifestations: 1. Reduction of erythrocytes maintenance in unit of blood volume – in men is lower than 4×10 12, in women is lower than 3,5×10 12 in 1L of blood; 2. Reduction of hemoglobin concentration – in men is lower than 130 g/l, in women is lower than 120 g/l; 3. Reduction of hematocrit – in men is lower than 0,43 l/l, in women is lower than 0,40 l/l; 4. Change of a color index – is not lower than0,85 and not higher than 1,15.

Qualitative changes of anemias: 1. Regenerative, but not mature forms of erythrocytes; 2. Degenerative changes of erythrocytes; 3. Cells of pathological regeneration. Regenerative forms of erythrocytes (cells of physiological regeneration) are young immature cells of red blood appearance of which in peripheral blood testifies about regeneration of cells erythroid lines in red bone marrow.

Regenerative forms include: а) reticulocytes. They are found in smear of blood after supravital staining. Represent denuclearized cells dirty – staining colouring with black inclusions as granules (substantia granulofilamentosa). In norm their contents in blood is 0,2-2 %. At the strengthened regeneration of cells red of the blood their quantity may increase 50 %. b) polychromatophils. They are found in blood smear stained by Romanovsky-Gimza method. That are denuclearized cells. Therefore polychromatophils different from mature erythrocytes by cyanotic shade of the colouring. In essence reticulocytes and polychromatophils are same cells in maturity – direct predecessors of erythrocytes.

Reticulocytes

c)normocytes (basophilic, acidophilic, polychromatophilic). They are nuclear predecessors of erythrocytes. In norm its absent in peripheral blood, and contain only in a red bone marrow. At the intensification of regeneration of cells erythroid lines may occur in blood as acidophilic and polychromatophilic rarely as basophilic normocytes. Sometimes erythroblasts can be found in blood (predecessors of normocytes) during hyperregenerative anemias. Degenerative forms of erythrocytes: а) anisocytosis – change in the size of the erythrocytes. Occurrence macrocytes and microcytes;

b) poikilocytosis – changed in the form of the erythrocytes. In conditions of the pathology may occur pear-shaped, extended, sickle-cell, oval erythrocytes, and also erythrocytes with the spherical form (spherocytes); c) changed in the staining of the erythrocytes, that depends on the contents of hemoglobin in them. Erythrocytes intensively colored are named hyperchromatic, with pale staining – hypochromatic. d) presence of pathological inclusions. They include Jolly’s bodies – are the rests of nuclear substance; Cabot’s rings – the rests of nuclear environment having the form of ring or eight; basophilic granularity – the rests basophilic substances of cytoplasm significative of toxic defeat of red bone marrow.

Poikilocytosis

Tear drop forms of erythrocytes

Basophilic stippling

Jolly’s body

Cells of pathological regeneration: а) megaloblasts are big cells with basophilic, polychromatophilic or acidophilic cytoplasm, containing large, located usually eccentrically nucleus with soft chromatin net; b) megalocytes – denuclearized cells which are formed during maturing of megaloblasts. They usually intensively stained, some the oval form, without enlightenment in the central part. Occurrence of the specific cells in red bone marrow and blood is typical for megaloblastic anemias, in particular of the B 12 -deficiency anemia.

Classifications of anemias І. According to colour index: а) normochromic (the colour index is within the limits of 0,85-1; for example, acute posthemorrhagic anemia during first days after hemorrhage); b) hypochromic (the colour index is lower than 0,85; for example, irondeficiency anemia); c) hyperchromic (the colour index is higher than 1,0; for example, B 12 -deficiency anemia).

ІІ. Pathogenetic classification: А. Posthemorrhagic anemias: a) acute posthemorrhagic anemia; b) chronic posthemorrhagic anemia. B. Hemolytic anemias. 1. Acquired: а) toxic-hemolytic; b) immune; c) mechanical; d) acquired membrane pathy. 2. Hereditary: а) hereditary membrane pathy; b) enzymopathy; c) hemoglobinopathy. C. Anemias as a result of erythropoiesis disorders. 1. Deficient: а) irondeficient; b) B 12 -deficient; c) proteindeficient. 2. Hypo-, aplastic. 3. Metaplastic. 4. Dysregulative.

The characteristic of posthemorrhagic anemias Posthemorrhagic anemia develops as a result of hemorrhage. Acute posthemorrhagic anemia arises after fast massive hemorrhage as a result wounding of vessels or their damage by pathological process. Chronic posthemorrhagic anemia develops after repeated hemorrhages, caused by injury of blood vessels during number diseases (dysmenorrhea, stomach ulcer, hemorrhoids etc.)

The picture of blood in acute posthemorrhagic anemias depends on time which has passed after hemorrhage. Depending on it is possible pick out three periods, each of them is characterized by the certain picture of peripheral blood. 1. The first several hours after acute hemorrhage. At this period of time the total amount of blood, and also total number of erythrocytes in an organism decreases. However in unit of blood volume the contents of erythrocytes and concentration of hemoglobin do not vary.

2. The period of time from several hours untill several days after acute hemorrhage. Dillution of blood takes place as a result of transition of liquid from interstitial spaces into blood vessels. As a result of it the quantity of erythrocytes and hemoglobin in unit of volume of blood decreases, as well as hematocrit. A color index stays without changes (normochromic anemia). 3. The period of time from several days untill 1-2 weeks after acute hemorrhage. The most typical feature of picture of blood in this period is occurrence of plenty regenerative forms of erythrocytes, due to amplification of erythropoiesis in red bone marrow. Because young unripe erythrocytes contain less hemoglobin in comparison with mature cells, the color index decreases also and anemia becomes hypochromic

Chronic posthemorrhagic anemia After the loss of iron hematologic signs of irondeficiency anemia develop: 1. Concentration of hemoglobin decrease; 2. Colour index decrease; 3. In blood smear there are degenerative forms of erythrocytes (micro- and poikilocytosis, hypochromy). 4. Quantity of erythrocytes and hematocrit may remain without changes.

The characteristic of hemolytic anemias Anemias which arise after destruction (hemolysis) of erythrocytes are called hemolytic. According to the mechanism of development hemolysis anemias may be: 1. Anemia with intravascular hemolysis; 2. Anemia with endocellular hemolysis. Intravascular hemolysis arises in blood vessels under the action of factors that damage erythrocytes. These factors are called hemolytic. They include: а) factors of physical nature (mechanical trauma, ionizing radiation, ultrasound, temperature); b) chemical agents (hemolytic poisons); c)biological factors ( agents of infectious diseases, toxins, enzymes); d) immune factors (antibodies).

Intravascular hemolysis it is accompanied by an output of hemoglobin from cells to blood plasma where it partially binds with protein haptoglobin. Endocellular hemolysis develops after absorption and digestion of erythrocytes by macrophages. In its basis the following reasons may be: а) occurrence of defective erythrocytes. b) occurrence on surface of erythrocytes the chemical groups capable to cooperate specifically with receptors of macrophages. In this case antibodydependent phagocytosis of erythrocytes is activated; c) hypersplenism – increase of phagocytic activity of spleen macrophages.

Acquired hemolytic anemias Depending on the reasons of development is allocated the following kinds of acquired hemolytic anemias. 1. Toxic hemolytic anemias. 2. Immune hemolytic anemias. 3. The anemias caused by mechanical damage of erythrocytes. 4. Acquired membranopathy.

Mechanical hemolysis of erythrocytes arises at prosthetics of vessels or valves of heart traumas of erythrocytes in capillaries of foot during a long march (marching hemoglobinuria), at their collision with strings of fibrin (microangiopathic hemolytic anemia of DIC- syndrome). Immune hemolytic anemias arise due to participation of specific immune mechanisms: а) receipt from the outside antibodies against own of erythrocytes (hemolytic desease of newborn); b) receipt into organism of erythrocytes which in plasma there are antibodies (the blood transfusion, not compatible on groups AB0 or Rh); c) fixing on a surface of erythrocytes foreing antigenes (haptens), in particular, medical products (antibiotics, sulfanilamides), viruses; d) formation of antibodies against own erythrocytes.

Toxic hemolytic anemia а) exogenous chemical agents: phenylhydrasin, lead, copper salts, arsenous hydrogen etc.; b) endogenous chemical factors: bile acids, products formed at burn desease, uremia; c) poisons of biological origin: snake, beer, poison of some kinds of spiders, aumber of infectious agents, in particular, hemolytic streptococcus, malarial plasmodium, toxoplasma, leishmania.

Acquired membranopathy arise due to the acquired defects of erythrocytes membranes. As an example may be paroxysmal noctural hemoglobinuria. This disease as a results of a somatic mutation erythropoietic cells with defects of membrane. Disorders of membranes are connected with changes of fat acids ratio which are part of their phospholipids. Erythrocytes of abnormal population get ability to fix complement and hemolyse. The picture of blood of acquired hemolytic anemias is characterized by reduction of erythrocytes quantity and hemoglobin. The color index in norm, however may be higher than 1 unit that is connected with extraerythrocytic hemoglobin. In blood smear the significant amount regenerative forms of erythrocytes is found out: reticulocytes, polychromatophils, normocytes.

Hereditary hemolytic anemias 1. Membranopathies. Defects of erythrocytes membranes 2. Enzymopathies. Anemias caused by disorder of erythrocytes enzymes. 3.Hemoglobinopathies. Arise after qualitative changes of hemoglobin. Hereditary membranopathies : 1) Membranopathies, caused by disorders of membrane proteins: а) microspherocytic anemia Minkovsky-Shoffar’s; b) ovalocytic hemolytic anemia;

Minkovsky-Shoffar’s anemia is hereditary, endoerythrocytic (membranopathy) hemolytic anemia with endocellular hemolysis. Type of inheritance – autosomal dominant. Hereditary defect is in membrane proteins of erythrocytes, in particular spectrin. Therefore permeability of erythrocytic membranes for ions sodium is considerably increased. Sodium and water transit from plasma inside of erythrocytes. In spleen they lose part of erythrocytes membrane and transform into microspherocytes. Life of erythrocytes decreases untill 8-12 days instead of 120.

Spherocytosis

Hereditary enzymopathies 1. Deficiency of pentose cycle enzymes. The most widespread enzymopathy is glucose-6- phosphatedehydrogenase deficiency anemia; 2. Deficiency of enzymes of glycolysis. The most widespread is deficiency of pyruvatekinase which results to disorders of energy provision Na-K- pumps of plasmatic membranes. Erythrocytes thus transform into spherocytes which are exposed to phagocytosis by macrophages; 3. Deficiency of enzymes of glutathion cycle (glutathionsynthetase, glutathionreductase, glutathionperoxidaza) results in oppression antioxidant systems of erythrocytes.

4. Deficiency of utilization АТP enzymes. An example is deficiency of proteines components Na-K- pump of erythrocytic membranes. Thus concentration of sodium that results them to hemolysis is increased in a cell. Qualitative and quantitative changes of hemoglobin lie in basis of development of hereditary hemoglobinopathies. The most widespread clinical form is sickle-cell anemia at which in β-chain of a molecule of hemoglobin glutamine acid is replaced on valine (HbS.) HbS is crystallized easily, erythrocyte loses its shape and cells of red blood get the sickle-like form. Macrophages phagocytose and hemolyse them, especially when hypoxia is present.

Sickle-cell anemia

Quantitative hemoglobinopathies are characterized by disorder of hemoglobin chains synthesis. An example of this group are α- and β-thalassemia. Thalassemias are hereditary caused hemolytic anemias with endocellular hemolysis. Pathological forms of hemoglobin which can easily drop out in deposit are appeared in the erythrocytes in α-thalassemia and erythrocytes liked targets (target cell anemia). Macrophages phagocyte and hemolyse the erythrocytes. Synthesis of β-chains of hemoglobin molecule disordered in β- thalassemia (disease of Cooley).

Thalassemia

Anemias as a result of erythropoiesis disorder The reasons of anemias with disorders of erythropoiesis may be: 1. Disorder of erythrocytes formation : deficiency of hemopoietic cells due to their damage or replacement, disorder of cell maturation (disorders of DNA resynthesis), defects of erythrocytes maturing and their go out into blood flow; 2. Disorders of hemoglobin synthesis: deficiency of iron, disorder of synthesis porphyrines (hereditary disorders of enzymes, poisonings by lead, deficiency of vitamin B6, synthesis disorder of protein chains of hemoglobin molecules).

Deficiency anemias Irondeficiency anemia arises as a result of: 1. Insufficient receipt of iron with organism: а) an alimentary anemia in the infants (feeding with cow or goat milk); b) disorder of iron absorbtion (resection of stomach, intestines, gastritises, enteritis); 2. Hemorrhage. It is the most widespread reason of iron deficiency in organism; 3. Strengthened use of iron – pregnancy, lactation. Insufficiency of iron in organism lead to disorder of feroproteins synthesis and the next disturbances: 1. Disorder of heme synthesis 2. Disorder of cytochromes formation and tissuel hypoxia

3. Decrease of catalase activity hemolysis of erythrocytes and development of dystrophic changes in cells. 4.Reduction of synthesis myoglobin and decrease(reduction) of resistance to hypoxia. Decrease of hemoglobin concentration in peripheral blood and reduction of colour index are typical for iron deficiency anemia. The quantity of erythrocytes decreases a little. In blood smear the quantity regenerative forms of erythrocytes (reticulocytes, polychromatophils) decreases and their degenerative forms (anulocytes, microcytosis, poikilocytosis) increase.

Irondeficiency anemia

Iron-deficiency anemia

Iron refractory anemia results from disorder of iron inclusion in heme at decrease of enzymes activity, which catalase synthesis of porphyrines and heme. The reasons may be: 1. Genetic defect of decarboxylase activity of coproporphyrinogen – the enzyme providing one of final stages of heme synthesis (it is inherited recessive, linked - X-chromosome); 2. Reduction of the maintenance pyridoxalphosphate – the active form of vitamin B 6 and as a result of this iron is not taken from mitochondria of erythroblasts and is not included in heme; 3. Lead blockade of sulfhydryl groups of the enzymes participating in heme synthesis.

B 12 -(folate)deficiency anemia. 1. Exogenous (alimentary) insufficiency – insufficient receipt in an organism with food. May develop in little children as a result feeding goat milk or dry dairy mixes. 2. Disorders of vitamin B 12 absorbtion: а) disorder of gastromucoprotein secretion (internal Castle’s factor). In case of hereditary atrophy of a mucous membrane of stomach, autoimmune damages of parietal cells of stomach, gastrectomy or resection of stomach; b) disorder of intestine function: chronic diarrhea (celiac disease, sprue), resection of the big parts of intestine; c) competitive use of vitamin B 12 by helmints and microflora of intestines (diphyllobothriasis).

3. Disorder of transcobalamines formation in liver. 4. Disorder of vitamin B 12 deposition in liver. 5. Increased use of vitamin B 12 (in pregnancy). Coenzyme forms of vitamin B 12 : 1. Methylcobalamine 2. 5-desoxyadenosilcobalamine. Effects of methylcobalamine deficit : In the bone marrow erythroblastic type of hemopoiesis is replaced on megaloblastic; Life duration of erythrocytes is shortened. Changes in cells of myeloid and megakaryocytic lines are shown by reduction of leukocytes quantity and thrombocytes, expressed atypia of cells (huge neutrophils, megakaryocytes with degenerative changes in a nucleus).

Atypic mitosis and huge cells of epithelium digestive tract; Development of inflammatory-atrophic processes in mucous membrane: Glossitis; Stomatitis Esophagitis Achylic gastritis Enteritis

B-12 deficiency anemia

B 12 -deficiency anemia - blood

B-12 deficiency anemia-b.marrow

B 12- deficiency anemia - bone marrow

Effects of 5-desoxyadenosilcobalamine deficit: 1. Accumulate propionic and methylmalonic acids, which are toxic for nervous cells. 2. Fatty acids with the changed structure are synthezised in nervous fibres cause disorder formation of myeline and damage of axones. 3. The degeneration changes of back and lateral columns of spinal cord develops (funicular myelosis), cranial and peripheral nerves are damaged.

Hypoplastic anemias Hypoplastic (аplastic) anemia is characterized by oppression hemopoietic functions of red bone marrow and shown by insufficient formation of erythrocytes, granulocytes and throrombocytes or only erythrocytes. There are acquired and is hereditary caused forms of hypoplastic anemia. The type of hereditary is autosomal- recessive type of inheritance concerns. The acquired forms may be caused by the following reasons: 1. Physical factors (ionizing radiation); 2. Chemical agents (benzene, lead, steams of mercury, medical products: cytostatic agents, chloramphenicol, sulfanilamids); 3. Biological factors (virus of hepatites).

1. Reduction of erythrocytes maintenance and concentration of hemoglobin when colour index is within of norm is characterised for the peacture of peripheral blood. 2. Regenerative erythrocytes (reticulocytes, polychromatophils ) are not found in a blood smear. 3. The maintenance of granulocytes (especially neutrophils) and thrombocytes decreases. 4. The quantity of lymphocytes may remain without changes. 5. In a red bone marrow the quantity of hemopoietic cells decreases with increase of maintenance of fatty tissue (picture of devastation red bone marrow). Because of iron is not used for the purposes hemopoiesis.

Appearence of hypoplastic anemias are connected with reduction of three kinds formation of form blood elements: erythrocytes, granulocytes and thrombocytes. It results in development of the following clinical syndromes: 1. The anemia and connected to it hypoxic syndrome. 2. Hemorrhagic syndrome. 3. The inflammatory processes caused by infectious agents (pneumonia, otitis, pyelitis etc.). Metaplastic anemias The metaplastic anemia is the result of hemopoietic tissue replacement on tissues: leucosis cells, connective tissue (fibrosis ), metastasises of tumor.

Dysregulative anemias Dysregulative anemias arise as a result of erythropoiesis regulation disorders (disorder of ratio between erythropoietins and inhibitors of erythropoiesis due to insufficiency of kidneys, damage of strome elements – microenvironments of erythropoietins cells, hypofunction of hypophysis, thyroid gland).

LEUКЕМІА Leukemia (leucosis) is a tumour, which arises from bloodforming cells and is primary damages bone marrow. The most characteristic signs of leucosis is the filling bone marrow by malignant cells of the local origin. It can be leucocytes and their predecessors, erythroblasts, megacaryoblasts.

Classification of leukemia 1. Acute leukemia 2. Chronic leukemia Acute leucosis is characterized disorder of bloodforming cells differentiation, do not go further ІV classes. The growth up of cells, which do not mature, lead to accumulation blast cells ІІ, ІІІ and ІV classes. They more and more take part of bone marrow at the expense of volume, which should be occupied normal hemopoietic elements.

FAB-classification created by French, American and British experts. It is constructed on stable morphological and cytochemical characteristics of leucosis cells. These characteristics reflect features them metabolism. According to modern conception all acute leucosis divide on two groups – myeloblast and lymphoblast. They are represented by many nosologic forms. Acute myeloblastic leucosis differentiate on five cytochemical signs – presence or absence in leucosis cells of the following substances: peroxidase, acid phosphatase, unspecific esterase, lipids and glycogen.

Classification of acute myeloblastic leucosis M 0 - acute undifferentiated leucosis M 1 - acute myeloblastic leucosis without signs of maturing (worse 3 % of promyelocytes) M 2 - acute myeloblastic leucosis with signs of maturing (over 3 % of promyelocytes) M 3 - acute promyelocytic leucosis (over 30 % of promyelocytes) M 4 - acute myelomonoblastic leucosis - over 20 % of promyelocytes M 5 - acute monoblastic leucosis M 6 - acute erythroblastic leucosis M 7 - acute megacaryoblastic leucosis

Acute myeloblastic leukemia

Chronical myelocytic leukemia

Classification of acute lymphoblastic leucosis 1.Acute leucosis of general type ( from cells-predecessors of B- lymphocytes ) 2. T-lymphoblastic leucosis 3. B-lymphoblastic leucosis.

Acute lymphoid leukemia

Chronical lymphoid leukemia

By FBA-classification acute leukemia is divided on groups L1, L2, L3. L1 – leukemia with predominance of small lymphoid cells L2 – leukemia with typical lymphoblasts L3 – macrolymphoblastic leukemia

Chronic leucosis differ from acute, that the cells bone marrow mature normally (up to VІ class), but proliferate in very plenty. 1. Chronic stage Illness represents a benign tumour and can be treatment. 2. The stage of accelerated development of illness Illness progresses toward malignisation. Control under dynamic of illness is lost. The treatment becomes all less effective. 3. The stage crisis of blastic cells Illness is exposed to radical transformation: chronic leucosis passes in acute (in 70 % - in acute myeloblastic, in 30 % - in acute lymphoblastic). Crisis of blastic cells approaches suddenly and becomes the reason of patients death.

Classification of chronic myeloid leukemia 1. Chronic myeloleucosis 2. Chronic monocytic leucosis 3. Chronic erythromyelosis 4. Chronic megacaryocytic leucosis 5. Eosinophilic leucosis

Acute myeloblastic leukemia – bone marrow

Classification of chronic lymphoid leukemia 1. B - cell leucosis 2. T - cell leucosis 3. Haircell leucosis

Hair-cell lymphoid leukemia

Etiology and pathogenesis of the leucosis On modern conception, leucosis arise on genetic, mutational basis. The question is about specific bloodforming cells mutation, which lead to superexpression of cell oncogenes, or protooncogenes. These genes are an integral part of cells genome and answer for proliferation of cells in norma. Cell oncogenes vitally are necessary. At the some time cell oncogenes have latent blastomogenic potentions. To major etiological factors, which capable to transform protooncogenes in active oncogenes are the chemical agents, ionising rays and retroviruses. It is know a few mechanisms of the cell oncogenes activation.

Mechanisms of protooncogene activation 1. Chromosomal aberrations 2. Genic amplification 3. Point mutations 4. Viral transduction 5. Insertional mutagenesis 6. Transactivation of transcription

Point mutations. Consider, that in most cases protooncogenes are activated as a result of structural changes them under influence of the chemical and physical agents. From chemical substances the most better is investigated benzol. There is an increased risk to be ill leucosis on productions, where is used benzol: 1. Chemical clearing of materials with use of the solvents benzolcontaining, 2. Production of film materials on the basis of rubber, paper and woodworking an industry. The mechanism of chemical leucosogenesis consists that chemical leucosogenes cause chromosomal and genes mutations. Some from these mutations seize cells oncogenes or them regulatory genes environment and initiate leucosis transformation of bone marrow cells.

Leucosogenic action of ionising rays. Increase of frequency leucosis took place after nuclear bombardment of Hiroshima and Nagasaki in The leucosis was fixed also in case of use ionising radiation with the medical purpose – in the patients with ancilosing spondilitis (Bechterev’s illness), myelomic illness, lymphogranulomatosis, autoimmune diseases, some dermatosis. The approximately % of cells, mainly lymphocytes, after therapeutical iradiation contain chromosomal aberrations as ring chromosomes, dicentric chromosomes and acentric of fragments. It is known leucosogenic action of radioactive isotopes. The radioactive phosphorum, which is used for treatment erythremia, caused acute leucosis in % of the patients.

Chromosomal aberrations. The precise correlation between localization of oncogenes and specific translocations of chromosomes is marked. It is established, that cell oncogenes frequently placed just in those sites chromosomes, where it is easy and naturally there are their breaks with consequent translocations of deleted fragments. The translocations can be original activators protooncogenes. To the present time in chromosomes of malignant cells more than 80 points are registered, where the breaks are observed. The analysis of distribution of these malignant spesific points and localization protooncogenes in genome of that person testify that the majority protooncogenes placed just in zones of specific breaks chromosomes.

Significant practical interest in the plan of the analysis of chromosomal role aberrations in activation of protooncogenes represent chromosomal and genes of illness, which are characterized by increased instability of chromosomes. To them belong Dawn’s illness, Fankony’s anemia, Blum’s syndrome, Louis-Bar’s syndrome and etc. It is established, that among patients with Dawn’s illness the frequency leucosis in 20 times is higher, than among persones without Dawn’s illness. Fankony’s anemia the diverse deviations karyotype from norm are found: chromatide breaks, acentric fragmentation, dicentric chromosomes, chromatide exchanges. In children with the Blum’s syndrome large percent of breaks chromosomes, as for want of Fankony’s anemia is observed.

Every type of leucosis are characterized specific chromosomal aberrations. The most better is investigated translocation 9/22, characterized for chronic myelocytic leucosis. This anomaly the first time was described in 1960 in Philadelphia (USA). Changed chromosome named philadelphian. That chromosome derivated in result reciprocal translocation between 9-th and 22-nd chromosome. Long shoulder of 9-th chromosome contains protooncogene abl (Abelson’s), which in mice causes leucosis, and long shoulder of 22-nd chromosome contains protooncogene sis, which causes sarcoma in haired monkeys.

Expression of Abelson’s oncogene in bone marrow to a cell stipulate appearance in it special oncoprotein with molecular weight 210 kD and by thyrosine activity. This oncoproteine is coded simultaneously Abelson’s oncogene from 9-th chromosome and site 22-nd chromosome, which adjoins to the point of break. The data about a role of chromosome aberrations in leucosis ethiology can be generalized as follows. The anomalies karyotype only when can cause leucosis, if they seize chromosome locuses, where are located protooncogenes. The activation stipulates these protooncogenes pathological proliferation and leucosis. Each chromosome has so-called fragile sites, which can be identified by means of differential colouring. Just here there are deletion, inversions and translocation, which become by the initiators of activation protooncogenes more often.

Virus transduction. On leucosogenic properties retroviruses divide on two groups – fast- transformed (viruses acute leucosis) and slow- transformed (viruses of chronic leucosis). Retroviruses of the acute leucosis differ by that their gene has an additional gene. It represents cells oncogene, which was snatched out from genome of cell and is built in virus RNA. Only now of it to name uncellular, and virus oncogene. Just this additional gene consider as the specific factor, which causes malignant transformation of a cell, and the process of massage cells oncogene through a virus is named virus transduction.

After repeated introduce in a cell virus (form cells) oncogene shows high propensity to expression. The reason, first of all, that it is seized by virus without surrounding regulatoring repressors genes. The second reason that a DNA- copy retrovirus is not absolutely exactly reading out return transcriptase. When the again created virus particles are introduced into the following cell, their DNA-copies with an additional gene (virus oncogene) are built in cell by the gene and easily expression – or because mutational virus oncogene becomes inaccessible repressoring gene to environment, or because this environment in general is absent.

Insertion of provirus. Most of viruses leucosis belongs not to fasttransformational, and to slowtransformational retroviruses. They do not contain oncogenes and induce experimental leucosis in an animal less effectively, than fasttransformational. Slowtransformational retroviruses cause transformation of cells because their DNA-copies are inserted in cells by a gene near to cells oncogene. The presence of another's DNA somehow activates cells oncogene up to very high level expression.

Genes amplification. This increase of copies of separate genes in reply to change of the external environment. In leucosis cells are detected amplificated of copy some protooncogenes. In itself amplification of oncogene does not concern to initiating events in leucogenesis. It is connected to a progression already of initiated cells. But in any case amplification of gene results in increase of level expressed RNA and precisely is proportional to level amplificated DNA.

Major chain of pathogenesis leucosis is oppression by leucosis cells normal hemopoiesis. Firstly, leucosis cell are capable produced in redundant amount colonialstimulation factor – stimulator of myelopoiesis. Secondly, this factor acts on leucosis cell stronger, than on the normal predecessors hemopoiesis.

Complete hematological picture of chronic leucosis. In the blood present as the maturing cells as an abundance cells of all classes – young, transition and mature. Hiatus leukemicus is absent. In particular, in blood of chronic myelocytic leucosis will be the next cells – predecessor ІІ and ІІІ classes, myeloblasts (ІV classes), cell V classes – promyelocytes myelocytes metamyelocytes sticknucleus neutrophils and mature cells of the VІ class (neutrophils). The picture of peripheral blood of chronic lymphocytic leucosis is characterized by the following features: there are a lot of mature lymphocytes, there are prolymphocytes and lymphoblasts, and also desroyed lymphoid cells (Gumprecht’s bodies or shadows of lymphocytes).

Clinical signs of leukemia 1. Metaplastic anemia 2. Thrombocytopenia and hemorrhagic syndrome 3. Inhibition of immune 4. Decrease of resistance to infectious agent