The effects of dietary T-2 toxin on acute herpes simplex virus type 1 infection in mice

Young male white Swiss mice were fed control diet or diet supplemented with 20 or 10 parts per million (ppm) of T-2 toxin for two or three weeks. These mice then were inoculated with herpes simplex virus type 1 (HSV-1) (9.6 x 10(6) plaque forming units) intraperitoneally. To compare the effects of T-2 toxin against a known immunosuppressive drug, cyclophosphamide was injected intraperitoneally at 150 mg/kg, 24 hours after treatment with HSV-1, into mice fed the control diet. Mice were necropsied and tissues were collected for microscopic and virologic examination. White Swiss mice which consumed a daily diet containing 20 ppm of T-2 toxin for two or three weeks were highly susceptible to HSV-1 infection and 27 of 36 (75%) died as a result of extensive hepatic and adrenal necrosis. Although HSV-1 was isolated from livers and brains of mice fed 20 ppm of T-2 toxin for two or three weeks, there was little or no inflammatory response found in the adrenals, livers, spinal cords, brains, or ganglia. The necrotizing encephalomyelitis observed in control mice was absent. High levels of dietary T-2 toxin appeared to be more immunosuppressive than cyclophosphamide because only one mouse died after treatment with HSV-1 and cyclophosphamide. Mice treated with cyclophosphamide had changes in brain, spinal cord, spleens, thymus, and bone marrow which were similar to those fed 20 ppm of T-2 toxin and infected with HSV-1, however, liver lesions were much less severe. HSV-1-infected mice on a diet with 10 ppm T-2 toxin had lesions of intermediate severity when compared with HSV-1-infected mice fed a diet with 20 ppm T-2 toxin and HSV-1-infected mice on control diets. Necrosis was less extensive in the livers and adrenals. The infrequent isolation of virus from liver and brain was consistent with the lack of intranuclear inclusion bodies and a more marked inflammatory response. Ten ppm of dietary T-2 toxin only depressed bone marrow and splenic red pulp to a mild or moderate degree. This may have enhanced the necrotizing encephalomyelitis observed in mice killed on days 6 and 8 after HSV-1 infection. Liver lesions were mild and those of the adrenals were moderate in mice fed control diet. The rare isolation of HSV-1 from the liver and brain and the findings of a moderate to severe necrotizing encephalomyelitis in these mice was consistent with an essentially functional immune system.     

Subacute toxicity of Dietary T-2 toxin in mice: influence of protein nutrition.

The subacute toxic effects of dietary T-2 toxin (20 ppm) incorporated in semipurified diets of 8%, 12% or 16% protein, were examined in young Swiss mice after one, two, three and four weeks. Dietary T-2 toxin caused substantial reductions in growth and food consumptaion, the degrees of which were greatest in mice fed the diets of reduced protein content. T-2 toxin consistently caused similar degrees of nonregenerative anemia, lymphopenia, thymic atrophy and gastric hyperkeratosis irrespective of the dietary protein level. However, erythroid hypoplasia was temporary in mice fed T-2 toxin in the 16%-protein diet such that erythroid precursors regenerated in splenic and bone marrow and were hyperplastic after four weeks. Liver to body weight ratios of mice fed T-2 toxin in the 16%-and 12%-protein diets increased during the four week trial in comparison to control mice fed at a similar rate. These observations indicated that suppression of erythropoiesis in mice by dietary T-2 toxin was temporarty and that the interval before regeneration was prolonged by diets of reduced protein content.     

Subacute toxic effects of dietary T-2 toxin in young mallard ducks.

Young Mallard ducks (Anas platyrhynchos) were fed diets containing purified T-2 toxin at levels of 20 or 30 ppm for two or three weeks. Ingestion of T-2 toxin was associated with reduced weight gain and delayed development of adult plumage. Affected ducks developed caseonecrotic plaques throughout the upper alimentary tract, especially in oropharynx and ventriculus. Several ducks also developed severe ulcerative, proliferative esophagitis and proventriculitis. Generalized atrophy of all lymphoid tissues consistently occurred. The manifestations of T-2 mycotoxicosis in Mallard ducks were mostly attributable to irritant toxicity to the alimentary mucosa. The T-2 toxin caused neither hematopoietic suppression nor a hemorrhagic syndrome in ducks. These alimentary lesions of T-2 mycotoxicosis in ducks do not resemble diseases of native waterfowl presently being recognized in routine surveillance of waterfowl mortality in Saskatchewan.     

Embryotoxic effects of prenatal T-2 toxin exposure in mice.

Pregnant CD-1 mice were administered T-2 toxin by gastric intubation on day 11 of gestation at dosages of 0, 0.75 and 1.5 mg/kg. The T-lymphocyte dependent antibody response against sheep red blood cells which was evaluated in the offspring at six weeks of age was not affected by T-2 toxin exposure. Individual birth and weaning weights were not influenced by T-2 toxin, but the litter size was reduced in the high dose group, without affecting the number of implantation sites per dam. The number of female offspring produced by dams exposed to 1.5 mg/kg T-2 toxin was less compared to other treatment groups, suggesting that the female fetus was more susceptible to embryolethal effects of prenatal T-2 toxin exposure. These results suggest that prenatal T-2 toxin exposure is unlikely to be a significant health problem with respect to primary humoral immunity. At the dosages given, T-2 toxin produced substantial embryotoxicity without alteration in antibody production. The embryolethal effects are a primary limiting factor which may preclude the expression of any immunoteratological manifestations associated with humoral immunity under natural field conditions.     

Determination of the acute 50% lethal dose T-2 toxin in adult bobwhite quail: additional studies on the effect of T-2 mycotoxin on blood chemistry and the morphology of internal organs

Three experiments were conducted to assess mortality rate, blood chemistry, and histologic changes associated with acute exposure to T-2 mycotoxin in adult bobwhite quail. In Experiment 1, adult quail were orally dosed with T-2 toxin to determine the lethal dose that resulted in 50% mortality of the affected population (LD50), and that dose was determined to be 14.7 mg of T-2 toxin per kilogram of body weight (BW). A second experiment was performed to study the effects of 12-18 mg/kg BW T-2 toxin on blood chemistry and liver enzyme profiles. Posttreatment uric acid, aspartate aminotransferase, lactic dehydrogenase, and gamma glutamyltransferase increased as compared with pretreatment values. In contrast, posttreatment plasma total protein, cholesterol, and triglyceride levels numerically decreased as compared with pretreatment values. Changes in blood chemistry values were consistent with liver and kidney damage after T-2 toxin exposure. In Experiment 3, histologic analyses of bone marrow, spleen, liver, small intestine, kidney, and heart were conducted on birds dosed in Experiment 2. Marked lymphocyte necrosis and depletion throughout the spleen, thymus, bursa, and gut-associated lymphoid tissue in the small intestine were observed in birds dosed with 15 and 18 mg/kg BW T-2 toxin. Necrosis of liver and lipid accumulation as a result of malfunctioning hepatocytes were also observed. Little or no morphologic change was observed in bone marrow and heart tissue. The LD50 for adult bobwhite quail as found in this study is two to three times higher than that reported for other species of commercial poultry. Results from these data confirm previous reports of immunosuppressive and/or cytotoxic effects of T-2 toxin in other mammalian and avian species. T-2 toxin may have a negative impact on the viability of wild quail populations.     

Experimental T-2 toxicosis in sheep.

Lambs received T-2 toxin at a rate of 0.6 or 0.3 mg/kg body weight per day in a protein reduced diet for 21 days to study the immunological and pathological effects of T-2 toxin in sheep. Blood was collected before T-2 treatment and on days 7, 14 and 21 of the trial for hematological and biochemical examination and for the separation of peripheral blood lymphocytes for the mitogen assay. Myeloid:erythroid ratios were determined from sternal bone marrow samples taken a day before T-2 treatment began, on day 12 and at death (day 22). Lambs treated with 0.6 mg/kg body weight of T-2 toxin daily were leukopenic on day 7 and lymphopenic on days 7 and 14. Also, on day 7, the mitogenic responses of these lambs to the B-cell mitogen, lipopolysaccharide, were significantly depressed and prothrombin times were prolonged. At necropsy, lymphoid atrophy of mesenteric lymph nodes and spleens was most marked in lambs treated with 0.6 mg/kg body weight of T-2 toxin per day. To the authors' knowledge, this is the first report of leukopenia, lymphopenia and lymphoid depletion in ruminants fed T-2 toxin.     

The effect of administration of a single dose of T-2 toxin on blood coagulation in the rabbit.

The single intravenous administration of T-2 toxin to rabbits at a dosage of 0.5 mg per kg body weight produced an alteration in several blood coagulation parameters. The activities of factors VII, VIII, IX, X and XI were decreased by approximately 40% six hours after T-2 toxin administration. Plasma fibrinogen concentration became elevated within 24 hours after T-2 toxin exposure. Circulating platelet numbers were unaffected by T-2 toxin administration. The similarity of coagulation parameter changes induced by T-2 toxin in animals receiving daily subcutaneous injections of vitamin K (0.5 mg per kg body weight) and those in nonvitamin K supplemented animals suggests that T-2 toxin does not function as a vitamin K antagonist.     

Pathology of adenoviral infection in turkeys (Meleagris gallopavo) with respiratory disease and colisepticemia.

Nuclear inclusion bodies typical of the adenovirus group were widespread in in the spleen and other tissues of 8-week-old turkeys with severe respiratory disease and concomitant evidence of colisepticemia. Adenoviral virions were seen in affected nuclei of splenic tissue and in negatively stained preparations of ground spleen. In splenic tissue, inclusions were most prominent in reticular cells and macrophages in the periarterial lymphoid sheaths, the red pulp and the marginal zones of the periarteriolar reticular sheaths. Marked reticuloendothelial hyperplasia, lymphoid atrophy and granulocytic splenitis characterized the splenic changes. There were inclusions in the respiratory tract, intestinal tract, liver, kidney and pancreas. Inoculation of young turkeys, especially when immunosuppressed, resulted in evidence of infection and respiratory disease. The viruses produced cytopathic changes in primary turkey kidney cell cultures but did not affect embryonating chicken eggs. Concentrated viral suspensions induced precipitin lines in agar gel immunodiffusion tests with known antisera against known turkey adenoviruses but did not show an antigenic relationship to chicken adenoviruses.     

Immunotoxic effects of T-2 mycotoxin on cell-mediated resistance to Listeria monocytogenes infection

The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice exposed to Listeria monocytogenes. Mice were inoculated with 4.0 X 10(5) (LD50) or 4.0 X 10(4) (nonlethal) L. monocytogenes on day 0 and treated orally on days 0, 1, 2, and 3 with 2.0, 1.0, or 0 mg/kg T-2 toxin. Toxin induced suppression of resistance was indicated by the rapid growth of Listeria in the spleen and by significant (P less than 0.005) increases in mortality due to listeriosis. Necrosis and depletion of lymphoid tissue, lymphopenia, and a marked decrease in the influx of lymphocytes and macrophages into Listeria elicited peritoneal exudates and at sites of infection in the liver and spleen occurred in the toxin treated mice. The immunotoxic effect of T-2 toxin on cell-mediated resistance to listeriosis was dosage dependent and attributed to toxin induced lymphoid depletion and the failure of surviving lymphocytes and mononuclear cells to clear the host of infection.     

Porcine circovirus type 2 in muscle and bone marrow is infectious and transmissible to naïve pigs by oral consumption

Pork products are a possible source of introduction of PCV2 isolates into a pig population. However, limited work has been done on the transmission through meat of porcine circovirus type 2 (PCV2), a virus associated with several disease syndromes in pigs. The objectives of this study were to determine if pork products from PCV2-infected pigs contain PCV2 DNA/antigen and to determine if the PCV2 present in the tissues is infectious by performing in vitro and in vivo studies. Skeletal muscle, bone marrow, and lymphoid tissues from pigs experimentally inoculated with PCV2 were collected 14 days post-inoculation (DPI). The tissues were tested for presence of PCV2 DNA by quantitative real-time PCR, for PCV2 antigen by immunohistochemistry (IHC), and for presence of infectious PCV2 by virus isolation and inoculation of PCV2 naïve pigs. Lymphoid tissues contained the highest amount of PCV2 (positive by PCR, IHC, and virus isolation), bone marrow contained a lower amount of PCV2 (positive by PCR and IHC but negative by virus isolation), and skeletal muscle contained the lowest amount of PCV2 (positive by PCR but negative by IHC and virus isolation). Naïve pigs fed for three consecutive days with either skeletal muscle, bone marrow, or lymphoid tissues all became PCV2 viremic as determined by quantitative real-time PCR on serum starting at 7 DPI. The pigs also seroconverted to PCV2 as determined by PCV2 IgM and IgG ELISA. In addition, PCV2 antigen was detected by IHC stains in lymphoid tissues and intestines collected from the majority of these pigs. Results from this study indicate that uncooked PCV2 DNA positive lymphoid tissues, bone marrow, and skeletal muscle from PCV2 viremic pigs contain sufficient amount of infectious PCV2 to infect naïve pigs by the oral route.     

T-2毒素研究进展

T-2毒素是污染我国饲料的主要霉菌毒素,主要危害动物的造血组织和免疫器官,引起出血性综合征,出现白细胞减少、贫血,使胃肠道功能受损等,对畜禽健康和畜牧业生产的危害很大.本文主要从T-2毒素的一般性质、产毒菌株、毒性效应、毒性机制及预防控制等方面作了论述.     

Regulation of murine macrophage phagocytosis of sheep erythrocytes by T-2 toxin

The effect of a single oral dose of 4 mg of T-2 toxin/kg of body weight on in vivo phagocytosis of sheep RBC by peritoneal macrophages was evaluated in nonsensitized mice and in mice sensitized with sheep RBC. T-2 toxin treatment had no effect on the viability or phagocytic activity of resident peritoneal macrophages in nonsensitized mice. However, a significant (P less than 0.005) increase in phagocytic activity occurred in cells from mice treated with toxin and subsequently sensitized with sheep RBC. In contrast, phagocytosis of sheep RBC was significantly (P less than 0.05) suppressed in cells from mice treated with toxin after sensitization. Toxin treatment induced necrosis of lymphocytes and significant decreases in thymus and spleen weights. Seemingly, T-2 toxin, administered at a dose that caused marked lymphoid depletion, suppressed or enhanced in vivo macrophage phagocytic activity in antigenically sensitized mice, and enhancement or suppression of phagocytosis was a function of the time of toxin treatment in relation to antigenic stimulation.     

Myelopoiesis and marrow adherent cells in estradiol-treated mice

Myelopoiesis and marrow adherent cells were evaluated in C57Bl/6J mice at two and four weeks after treatment with 0.1 mg 17 beta-estradiol cyclopentylpropionate. Estradiol-treated mice were lymphopenic and eosinopenic at two and four weeks; in addition, neutropenia occurred at four weeks. Numbers of lymphoid, granulocytic, and erythroid cells were decreased in the marrow at two and four weeks. The numbers of granulocyte-macrophage and fibroblast colony-forming units in the humeral marrow were also decreased at two and four weeks. However, the hematopoietic ability of marrow adherent cells was unchanged in estradiol-treated mice. Thymic cortical atrophy, metaphyseal osteosclerosis, and neutrophilic infiltration of the uterus occurred in estradiol-treated mice.     

Engraftment of severe combined immune deficient/beige mice with bovine foetal lymphoid tissues.

To develop a model of bovine thymus and lymph node growth in vivo, we have implanted bovine foetal tissues (16-23 weeks gestation) under the renal capsule of severe combined immune deficient (SCID)/beige (BG) mice and assayed for graft growth and characteristics 2-18 weeks after engraftment. Bovine foetal thymus and lymph node grew considerably following engraftment of SCID/BG mice. Growth was optimal if bovine foetal tissues were used before gestation Week 17. Bovine-mouse chimerism was confirmed using glucose phosphate isomerase analysis. Bovine thymus grew during the entire 18 weeks of study. Growth of bovine lymph node was initially rapid, reaching a maximum at 2 weeks after transplantation followed by a progressive decrease in size. Transplanted bovine lymph node and thymus were morphologically similar to age-matched bovine foetal tissue for a limited time period. Fibrosis, degeneration and depletion of lymphocytes were evident 6 weeks after engraftment; changes were more severe in lymph node than in thymus whereas increases in lymphocytes, lymphopoiesis and follicle formation were evident in age-matched bovine foetal tissue. Despite growth and morphological similarities of the transplanted tissue, blood counts suggested there was no peripheralization of bovine leucocytes. Bovine immunoglobulins (IgG1 and IgG2) were detected in serum of some SCID/BG chimeric mice for a limited time. The appearance of bovine immunoglobulins at 2 weeks in SCID/BG chimeric mice depended on the age of the foetal donor (> 18 weeks) and coincided with the appearance of morphologically mature lymphocytes in the donor foetus lymph nodes. The ability to produce bovine immunoglobulins decreased 8 weeks after engraftment, coinciding with the depletion of lymphocytes in the engrafted lymph node. Lymphocyte depletion and loss of function of engrafted tissues appear the result of a lack of lymphoid progenitors normally derived from hematopoietic stem cells in the bone marrow.     

生物素—亲和素法检测雏鸡实验性新城疫的研究

采用生物素—亲和素法检测实验鸡雏35只。结果,接毒12h,在法氏囊滤泡的髓质、胸腺小叶的髓质、脾白髓的脾小结、盲肠扁桃体的淋巴小结及弥散淋巴组织内首先出现核浓缩,胞浆呈棕色的阳性淋巴细胞。接毒1～3d,在骨髓血窦外区、法氏囊滤泡、胸腺小叶、脾白髓、盲肠扁桃体和弥散淋巴组织内出现核浓缩、碎裂,泡浆呈棕色的阳性淋巴细胞、阳性巨噬细胞和阳性网状细胞。接毒4～5d死亡病例的这些免疫器官原有结构破坏,形成蜂窝状空泡结构,空泡含有核碎屑和棕色微粒。肝、肾、肺的微血管充满红细胞凝集,其胞膜显现深棕色微粒。根据这些变化可建立雏鸡新城疫诊断。     

Enhanced resistance to listeriosis induced in mice by preinoculation treatment with T-2 mycotoxin

The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice challenge exposed with Listeria monocytogenes. Mice were treated orally on days -5, -4, -3, -2, -1, +1, and +3 with 2.0, 1.0, 0.5, or 0 mg of T-2 toxin/kg of body weight and were exposed to 10(6) (LD100) or 10(5) (LD50) L monocytogenes by intraperitoneal injection on day 0. Necrosis and depletion of lymphocytes in the thymus and spleen, decrease in thymus weight, reductions in the number of circulating total leukocytes and lymphocytes, and necrotizing gastroenteritis occurred in the toxin-treated mice. Although the cytotoxic effect of T-2 toxin on lymphoid tissue was marked, enhanced resistance to Listeria infection was revealed by significant (P less than 0.01) decreases in mortality caused by listeriosis in the toxin-treated mice. Mortality decreased from 100% to 64% in the mice exposed to 10(6) Listeria and from 50% to 20% in the mice exposed to 10(5) Listeria. Percentage of mortality after Listeria challenge exposure was dependent on the T-2 toxin dose and was progressively decreased in the mice given 0.5, 1.0, or 2.0 mg of toxin/kg.     

Acute toxicological experiment of T-2 toxin in rabbits

Rabbits were treated with a single oral dose (1, 2, 4, 6, 8, 10 or 15 mg/kg body mass) of T-2 fusariotoxin. Doses of 4 mg or higher killed the animals in 24 to 48 h. As opposed to the controls, in the treated rabbits gross pathological and histopathological examinations revealed acute catarrhal gastroenteritis, necrosis of lymphoid cells of the gastrointestinal mucosa, centrolobular dystrophy of the liver, necrosis of cells of the mononuclear phagocyte system (MPS) in the liver, tubulonephrosis, focal dystrophy of the adrenal cortex, lymphocyte depletion involving both T- and B-cell-dependent zones of the lymphoid organs (spleen, lymph, ampulla ilei), and depletion and necrosis of the myelopoietic cell colonies of the bone marrow. Similar but milder changes were observed in surviving rabbits exsanguinated 48 h after treatment. In addition to the direct damage done to the digestive tract mucosa and liver, the toxin severely damaged the cells participating in humoral and cell-mediated immunity and in the local defence of the intestinal mucosa, and markedly impaired phagocytosis and granulocytopoiesis. In another experiment rabbits were given oral doses of 2 mg/kg body mass T-2 toxin daily for several days. One rabbit was killed by bleeding every day. In rabbits killed beyond day 7 there was subacute catarrhal gastritis, emaciation, and hypertrophy of the adrenal cortex.     

Immunopathological effects of experimental T-2 mycotoxocosis in broiler chicken co-infected with infectious bronchitis virus (IBV)

A total of 128 1-week-old chicks were classified into four groups; T-2 toxin fed (T-2), IBV infected (IBV), T-2 toxin fed and co-infected with IBV (T-2+IBV), and untreated (control) for a period of 6 weeks. Within their respective groups, the birds belonged to T-2 and T-2+IBV were exposed to 2 ppm of T-2 toxin contaminated feed for 6 weeks, and 0.2 ml of 10 EID(50) (10(5.69)/0.2 ml) inoculums of IBV isolate (India/LKW/56/IVRI/08) was used to challenge the chicks belonged to IBV alone and T-2+IBV groups after 3 weeks of the experiment. To study immunopathological effects, parameters such as lymphocyte stimulation indices (SI), haemagglutination inhibition, enzyme linked immunosorbant assay (ELISA), peripheral lymphocytes CD(4)(+) and CD(8)(+) analysis, and histopathological examination of lymphoid organs were done. Accordingly, SI values were significantly (P<0.05) lower in all the treatment groups as compared to control, however, the SI values of IBV infected group were significantly higher than the values in toxin fed groups. The mean HI titres to ND vaccine was significantly (P<0.05) lower in the toxin groups at all the intervals, and the antibody titres in IBV infected group were significantly (P<0.05) higher than that of T-2 toxin fed and co-infected with IBV group but were significantly (P<0.05) lower than the control at 21 (3) and 28 (10) days of toxin feeding (DTF) (days post infection (DPI)). Similarly, the mean IBV ELISA antibody titres in the toxin fed groups were significantly (P<0.01) reduced as compared with the IBV ELISA antibody titres of IBV infected but not toxin fed group, at all intervals. Peripheral CD(4)(+):CD(8)(+) ratios in T-2+IBV group and number of CD(4)(+) and CD(8)(+) peripheral lymphocytes in all treatment groups were significantly reduced as compared to the values in control birds. However, CD(4)(+):CD(8)(+) ratios of IBV infected group at 42 (21) DTF (DPI) were found significantly (P<0.05) higher than the values in control birds. Histopathologically, lymphoid organs (bursa of Fabricius, spleen, thymus, caecal tonsils and Harderian glands) showed moderate to severe necrosis (lymphocytolysis) and extensive lymphocyte depletion in all the toxin groups (T-2 and T-2+IBV groups) where the severity and extent of the lesions were more in T-2+IBV group. The findings of the present experiment revealed immunosuppressive effects of T-2 toxin and aggravated the pathology and pathogenesis of IBV infection.     

Pancytopenia Secondary to Lymphoid Leukemia in Three Horses

Pancytopenia was observed in two 3-year-old geldings and one 11-year-old mare. All horses had a brief history (2 days to 4 weeks) of fever, anorexia, and depression. One of the three horses had blast cells present on a peripheral blood smear. Examination of the bone marrow showed substantial infiltration with neoplastic lymphoid cells. At necropsy, neoplastic cells were restricted to the bone marrow in one horse, present in bone marrow, liver, and spleen in the second horse, and reported in multiple tissues in the third horse, including bone marrow, kidneys, lung, myocardium and lymph nodes. The value of a bone marrow aspirate and core biopsy in the investigation of pancytopenia is highlighted. (Journal of Veterinary Internal Medicine 1993; 7:360–363. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Recognition and classification of dysmyelopoiesis in the dog: a review

Dysmyelopoiesis is defined as a hematologic disorder characterized by the presence of cytopenias in the blood and dysplastic cells in one or more hematologic cell lines in the blood or bone marrow. The causes of dysmyelopoiesis include acquired mutations in hematopoietic stem cells (i.e., myelodysplastic syndromes [MDSs]), congenital defects in hematopoiesis, and dysmyelopoietic conditions associated with various disease processes, drug treatments, or toxin exposure. Two major subtypes of MDSs (i.e., MDS with refractory cytopenias and MDS with excess myeloblasts) have been described that differ in clinical presentation, response to treatment, and survival time. The most frequently occurring causes of secondary dysmyelopoiesis include immune-mediated hematologic diseases, lymphoid malignancies, and exposure to chemotherapeutic drugs. Differentiation of the various causes of dysmyelopoiesis is essential for establishing an appropriate therapeutic plan and for determining prognosis.