Immune-mediated hemolytic anemia and pure red cell aplasia in a Jack Russell Terrier during treatment for hypoadrenocorticism.

An 11-year-old neutered male Jack Russell Terrier was presented to Yuki Animal Hospital for regenerative anemia during the treatment of hypoadrenocorticism. A blood smear examination showed spherocytes, polychromatic erythrocytes, and erythrocyte ghosts. The direct agglutination test was positive at 37°C. The dog was then diagnosed with immune-mediated hemolytic anemia (IMHA). Although prednisolone and mycophenolate mofetil were administered, the hematocrit and reticulocyte count decreased, and nonregenerative anemia developed. A bone marrow examination was performed to diagnose the cause of the nonregenerative anemia. Histologic and cytologic bone marrow examination revealed a normocellular to hypercellular medulla with severe erythroid hypoplasia. No proliferation of lymphocytes or lymphoblast-appearing cells was observed. This dog was diagnosed with pure red cell aplasia (PRCA). Despite treatment with immunosuppressive agents, the patient died of thrombosis. Although these associations were unclear, this is the first report of PRCA diagnosis following IMHA and while treating hypoadrenocorticism.

Suspected primary pure red cell aplasia in a 4-month-old intact male mixed breed Bernese mountain dog.

A 4-month-old, 31-kg intact male mixed-breed Bernese mountain dog was presented for evaluation of severe non-regenerative anemia after several days of lethargy, inappetence and pale mucous membranes. Bone marrow evaluation and complete response to immunosuppressive therapy were suggestive of primary pure red cell aplasia (PRCA). Primary PRCA is a rare immune-mediated non-regenerative anemia that is overrepresented in middle-aged to older spayed female dogs and has not previously been described in an intact male puppy.

Aplasie primaire pure des globules rouges suspectée chez un bouvier bernois mixte mâle intact âgé de 4 mois. Un bouvier bernois mixte mâle intact âgé de 4 mois et pesant 31 kg a été présenté pour l'évaluation d'une anémie grave non régénérative après plusieurs jours de léthargie, d'inappétence et de muqueuses pâles. L'évaluation de la moelle osseuse et la réponse complète au traitement immunosuppresseur suggéraient une aplasie primaire pure des globules rouges (PRCA). L'érythroblastopénie primaire est une anémie non régénérative à médiation immunitaire rare qui est surreprésentée chez les chiennes stérilisées d'âge moyen à plus âgées et qui n'a pas été précédemment décrite chez un chiot mâle intact.(Traduit par Dr Serge Messier).

Use of Nandrolone Decanoate in Treatment of Pure Red Cell Aplasia Secondary to Diclofenac Administration: A Case Report.

Pure red cell aplasia (PRCA) is a disorder that leads to a nonregenerative anemia that results from erythroid precursors failing to reach maturity in the bone marrow, whereas the numbers of mature myeloid and megakaryocytic cells remain normal. PRCA can be induced by autoimmune processes, infections, drugs, toxins, and radiation, and is diagnosed by a bone marrow cytology examination after excluding the most common causes of nonregenerative anemia. Immunosuppressive therapies are used to treat PRCA, and usually involve the use of glucocorticoids, cyclosporin, or azathioprine. Alternatively, although little studied in veterinary medicine, drugs which stimulate bone marrow (e.g., nandrolone decanoate) have been mentioned as possible therapeutic agents. A case of PRCA that presented at the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine and Animal Science (UNESP)-Botucatu, Brazil showed a good therapeutic response to weekly administration of nandrolone decanoate. Therefore, it was concluded that bone marrow stimulants might improve the quality of life of PRCA patients, provided they are used with caution and under close clinical supervision.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

BACKGROUND: Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. OBJECTIVES: The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. METHODS: Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. RESULTS: Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. CONCLUSIONS: Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis.

The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs.

BACKGROUND: Darbepoetin alfa (darbepoetin) is an erythropoiesis-stimulating agent used for the treatment of anemia secondary to chronic kidney disease (CKD) in dogs, but reports describing response are lacking. HYPOTHESIS/OBJECTIVES: To evaluate the effectiveness of darbepoetin in dogs with anemia secondary to CKD, dosing protocols, and adverse events. ANIMALS: Thirty-three client-owned dogs with naturally occurring CKD, including 26 with comorbidities. METHODS: Multi-institutional retrospective study. RESULTS: The median starting dosage and highest dosage of darbepoetin administered were 0.5 and 0.8 µg/kg SC once weekly, respectively. Response to treatment was defined as achieving a packed cell volume (PCV) ≥30% or an increase in PCV ≥10%. Twenty-eight of 33 dogs (85%) achieved a PCV ≥30% and 22 of 33 (67%) dogs achieved an increase in PCV ≥10%. Median time to achieve a PCV ≥30% was 29 days. A higher starting dosage was associated with achieving an increase in PCV ≥10% (P = .01). No dog sustained a response at a dosing interval >q21d. Potential adverse events included increased blood pressure requiring treatment (n = 12), seizures (n = 5), vomiting (n = 3), diarrhea (n = 3), and possible pure red cell aplasia (PRCA) (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Darbepoetin, when combined with treatment of comorbidities, is an effective treatment for anemia secondary to CKD in dogs. A dosing interval >q21d was ineffective at maintaining a response to treatment. PRCA was a possible adverse event in 2 of 33 dogs (6%).

Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten.

A 9-month-old, female, domestic longhair cat with severe anaemia tested positive for feline leukaemia virus (FeLV) and was humanely destroyed and submitted for necropsy examination. Gross findings included a non-divided rostral telencephalon, consistent with semilobar holoprosencephaly. Histological examination of the bone marrow revealed an almost complete absence of erythroid precursor cells, consistent with pure red cell aplasia, and mild to moderate myelofibrosis. This case demonstrates a very unusual central nervous system defect, as well as an atypical presentation of pure red cell aplasia, in a FeLV-positive kitten.

Feline non-regenerative immune-mediated anaemia: features and outcome in 15 cases.

OBJECTIVES: Pure red cell aplasia (PRCA) and non-regenerative immune-mediated haemolytic anaemia (NRIMHA) are uncommon causes of non-regenerative anaemia affecting the bone marrow in the cat. This retrospective study aimed to describe the clinical features, treatment and outcome (remission and survival) of cats with these disorders. METHODS: Cases of PRCA and NRIMHA presenting between 2009 and 2013 were retrieved. Clinical features including signalment, history, clinical signs and diagnostic investigations were recorded, as well as treatment(s) used and outcome (remission and survival). Outcome was compared for PRCA and NRIMHA. RESULTS: Fifteen cats met inclusion criteria: seven with PRCA and eight with NRIMHA. The majority (12/15) were younger than 3 years of age. Volume overload was common (8/11). Treatment with whole blood transfusions with or without Oxyglobin was necessary in most cats (14/15) and resulted in congestive heart failure in one cat. Most cats (11/15) achieved remission 12-42 days after starting immunosuppressive treatment. Treatment protocols associated with remission were glucocorticoids alone (remission in 6/7 cats), glucocorticoids and chlorambucil (remission in 3/6 treated cats), glucocorticoids and ciclosporin (one cat only) and ciclosporin alone (one cat only). Relapse was observed in 3/11 cats, and 8/11 cats were still receiving treatment at the time of follow-up. Outcome (remission and survival) did not differ between PRCA and NRIMHA. CONCLUSIONS AND RELEVANCE: PRCA and NRIMHA are uncommon causes of anaemia in predominantly young cats. The prognosis is reasonable, with a mortality rate of 27%, and it can take at least 6 weeks before remission is observed. Following clinical remission, gradual withdrawal of immunosuppressive treatments should be attempted, with close monitoring for relapse; some cats may require long-term treatment. This study is the first to report the use of chlorambucil as an adjunctive immunosuppressant in these cases. Outcome did not differ for PRCA and NRIMHA.

Clinical use of cyclosporine as an adjunctive therapy in the management of feline idiopathic pure red cell aplasia.

The clinical use of cyclosporine is described in a group of client-owned cats diagnosed with idiopathic pure red cell aplasia (PRCA). All 10 cats were treated with combinations of glucocorticoids and cyclosporine. Of the 10 cats, the eight for which follow-up data was available achieved and maintained remission for a median of 31 and 406 days, respectively. Therapy was reduced or discontinued in 7/8 cats; 2/7 maintained remission off therapy and 5/7 cats relapsed. Remission was reinduced in four cats, with 3/4 cats maintained long-term on low dose therapy. Adverse effects associated with cyclosporine therapy were responsive to dose reduction or drug withdrawal. Feline idiopathic PRCA was responsive to combination immunosuppressive therapy with glucocorticoids and cyclosporine. Relapse was common, particularly after drug discontinuation; therefore, most cats required maintenance long-term low dose therapy.

Immune-mediated pure red cell aplasia in a domestic ferret.

CASE DESCRIPTION: An 8-month-old spayed female domestic ferret (Mustela putorius furo) was referred for examination to determine the cause of lethargy and severe anemia. CLINICAL FINDINGS: Initial examination revealed that the ferret was lethargic but with appropriate mentation. The only other abnormal findings were severe pallor of the mucous membranes, nasal planum, and skin and a PCV of 8%. Pure red cell aplasia (PRCA) was diagnosed on the basis of cytologic evaluation of a bone marrow biopsy specimen. TREATMENT AND OUTCOME: Medical treatment included blood transfusions, IM administration of iron dextran, oral administration of antimicrobials and gastrointestinal tract protectants, and SC administration of erythropoietin. Once PRCA was diagnosed, the ferret was orally administered prednisone, cyclosporine, and azathioprine. Nine months after onset of treatment, the PRCA was in remission and the ferret was doing well. Immunosuppressive treatment was discontinued at 14 months after onset of treatment, and 36 months after initial examination, the ferret appeared to be healthy. CLINICAL RELEVANCE: It is important that PRCA be considered as a differential diagnosis for a ferret with severe anemia. Prolonged immunosuppressive treatment was successful in the ferret described here.

Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

Immune-mediated erythroid and megakaryocytic aplasia in a cat.

CASE DESCRIPTION: A 6-month-old domestic shorthair cat was evaluated because of acute lethargy. CLINICAL FINDINGS: Severe nonregenerative anemia and thrombocytopenia were identified. Cytologic examination of a bone marrow aspirate revealed selective erythroid and mega-karyocytic aplasia and a high number of apparently normal small lymphocytes. Infectious agents implicated in feline hematologic disorders were excluded on the basis of serologic tests or PCR amplification, including FeLV, Ehrlichia canis, Anaplasma phagocytophilum, Mycoplasma haemofelis, Candidatus Mycoplasma haemominutum, and Candidatus Myco-plasma turicensis. TREATMENT AND OUTCOME: A 10-day course of prednisolone administration did not improve the hematologic disorder. Administration of human polyclonal immunoglobulins preceded increased reticulocyte count by 3 days. A second bone marrow examination confirmed restoration of erythroblasts and megakaryocytes. After 1 relapse, the disease was successfully controlled with prednisolone for > 3 years. CLINICAL RELEVANCE: Immune-mediated bone marrow aplasia is rare in cats and usually affects only erythrocyte progenitors. Concomitant involvement of erythroid and megakaryocytic cell lines can be successfully treated via immunosuppressive therapy. Human immunoglobulins seem to be well tolerated in cats; however, proof of a beneficial effect requires further study.

Differentiating benign and malignant causes of lymphocytosis in feline bone marrow.

Differentiation of benign and malignant causes of lymphocytosis in blood or bone marrow can be problematic. In the present study, reports of examinations of bone marrow from cats, submitted over an 8-year period, were reviewed to identify cats with increased numbers of small lymphocytes. Of 203 reports reviewed, 12 (5.9%) indicated increased numbers of small lymphocytes. Diagnoses for these cats included chronic lymphocytic leukemia (CLL; n = 2), pure red cell aplasia (PRCA; n = 4), immune-mediated hemolytic anemia (IMHA; n = 3), thymoma (n = 1), cholangiohepatitis (n = 1), and fever of unknown origin (n = 1). Several factors were identified that could be used to differentiate reactive lymphocytosis from CLL. Cats with CLL tended to be older, and lymphocytes were slightly larger and had cleaved or lobulated nuclei. Reactive lymphocytosis was associated with immune-mediated anemias and inflammatory diseases. In reactive lymphocytosis, the proliferating lymphocytes were organized into lymphoid aggregates in bone marrow and were predominately B cells. Alternatively, in CLL and thymoma, the proliferating lymphocytes were diffusely distributed and were predominately T cells. Therefore, differentiation of the causes of lymphocytosis should include evaluation of signalment, concurrent disease conditions, lymphocyte morphology, lymphocyte distribution in bone marrow, and immunophenotype. Cat age, presence of severe anemia, and evidence of inflammatory disease also should be considered.

Primary pure red cell aplasia in dogs: 13 cases (1996-2000).

OBJECTIVES: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA). DESIGN: Retrospective study. ANIMALS: 13 dogs with severe nonregenerative anemia and bone marrow erythroid aplasia. PROCEDURES: Medical records of dogs determined to have PRCA on the basis of results of blood and bone marrow analysis between 1996 and 2000 were reviewed. Criteria for inclusion in the study were severe nonregenerative anemia (Hct < 20%; reticulocyte count < 1.0%), selective erythroid aplasia in bone marrow, and lack of underlying diseases that may have caused the anemia. RESULTS: Median age of dogs was 6.5 years. Females were significantly overrepresented. Median Hct was 10%, and median reticulocyte count was 0.1%. Direct Coombs' test results were negative for all dogs tested, and spherocytosis was evident in 2 dogs. All dogs were treated with prednisolone, and 2 dogs were treated with prednisolone and cyclophosphamide. Responses to treatment were complete, partial, and poor in 10, 1, and 2 dogs, respectively. Median time required to achieve an increase of 5% or more in Hct was 38 days, and median time to complete remission was 118 days. Of 10 dogs for which follow-up information was available, only 1 required long-term immunosuppressive treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with PRCA appear to respond readily to treatment with immunosuppressive drugs; however, hematologic responses may not be observed for weeks to months after initiation of treatment.

Clonality analysis of various hematopoietic disorders in cats naturally infected with feline leukemia virus.

The clonality analysis of the bone marrow cells was carried out by detecting the integrated proviruses of feline leukemia virus (FeLV) to understand the pathogenesis of FeLV-associated hematopoietic disorders in cats. Bone marrow cells from 4 cases with acute myeloid leukemia (AML), 9 cases with myelodysplastic syndromes (MDS), 2 cases with pure red cell aplasia (PRCA) and 3 healthy carriers infected with FeLV were subjected to Southern blot analyses using an exogenous FeLV probe. Clonal hematopoiesis was found in all the cases with AML and in 6 of the 9 cases with MDS, but not in the cases with both PRCA and healthy carriers infected with FeLV. In the 2 cases with MDS, it was thought that the same clones of the hematopoietic cells might proliferate before and after the progression of the disease irrespective of the changes of the hematological diagnoses by cytological examination. This study indicates that MDS in cats is a disease manifestation as a result of clonal proliferation of hematopoietic cells and can be recognized as a pre-leukemic state of AML.

Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999).

OBJECTIVE: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA) and idiopathic nonregenerative immune-mediated anemia (NRIMA). DESIGN: Retrospective study. ANIMALS: 43 dogs with severe nonregenerative anemia. PROCEDURE: Medical records of dogs determined to have PRCA, NRIMA, or ineffective erythropoiesis on the basis of bone marrow analysis between 1988 and 1999 were reviewed. Criteria for inclusion were > or = 5-day history of severe nonregenerative anemia (Hct < 20%; < 60.0 x 10(3) reticulocytes/microliter) with no underlying diseases. Information was retrieved on signalment, clinical signs, laboratory test results, treatment, and outcome. RESULTS: Median age of the dogs was 6.5 years. Spayed females and Labrador Retrievers were significantly overrepresented. Median Hct was 11% with no evidence of regeneration (median, 1.5 x 10(3) reticulocytes/microliter). Direct Coombs' test results were positive in 57% of dogs. Biochemical abnormalities included hyperferremia and high percentage saturation of transferrin. Bone marrow findings ranged from PRCA (5%) to erythroid hyperplasia (55%). Myelofibrosis was common. Dogs were treated with immunosuppressive drugs and the response was complete, partial, and poor in 55, 18, and 27% of the dogs, respectively. Mortality rate was 28%. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered in dogs with severe, nonregenerative anemia, normal WBC and platelet counts, hyperferremia, mild clinical signs, and no evidence of underlying disease. Bone marrow findings range from the rare PRCA to erythroid hyperplasia. Myelofibrosis is often detected in affected dogs and may prevent bone marrow aspiration.

Pure red cell aplasia in cats: 9 cases (1989-1997).

OBJECTIVE: To evaluate clinical features, laboratory test results, treatment, and outcome of FeLV-negative cats with pure red cell aplasia (PRCA) diagnosed by examination of bone marrow. DESIGN: Retrospective study. ANIMALS: 9 cats. PROCEDURE: Medical records and smears of bone marrow aspirates were reviewed to determine clinical features, laboratory test results, treatment, and outcome of this syndrome in cats. RESULTS: PRCA was diagnosed in 9 cats that were between 8 months and 3 years old. Cats had 2- to 16-day histories of lethargy and anorexia, and a severe normocytic, normochromic to hypochromic, nonregenerative anemia (Hct range, 6 to 15%; reference range, 25 to 45%). Other hematologic values were generally within reference ranges. Consistent changes in biochemical profiles included high aminotransferase activities and hyperferremia. Cats were seronegative for FeLV and feline immunodeficiency virus. Smears of bone marrow aspirates were characterized by absence of identifiable erythroid precursors and a high proportion of small lymphocytes. Abnormalities were not identified in megakaryocytes or myeloid cells. Treatment with immunosuppressive drugs (corticosteroids and cyclophosphamide or cyclosporin) resulted in resolution of anemia within 3 to 5 weeks. Most cats required long-term treatment to maintain Hct within reference range and tended to relapse when treatment frequency or dosage was decreased (especially if done rapidly) or treatment was discontinued. CLINICAL IMPLICATIONS: PRCA is a rare syndrome in young FeLV-negative cats, and is characterized by severe nonregenerative anemia and absence of erythroid cells in bone marrow. The condition requires prompt, aggressive, often long-term treatment with immunosuppressive drugs for resolution.

[Cyclosporin A therapy in a cat with pure red cell aplasia]. / Cyclosporin-A-Behandlung einer Katze mit selektiver Aplasie der Erythropoese.

The case of a one year and 7 months old castrated male cat suffering from severe, non regenerative anaemia (packed cell volume: 8.6%; reticulocyte count: 1/1000) is presented. A combined ELISA-test for feline leukaemia virus antigen and antibodies against feline immunodeficiency virus was negative. Using indirect Coomb's test IgM as well as the complement component C3b could be demonstrated on the erythrocytes. Cytological investigation of the bone marrow revealed a selective, nearly complete aplasia of the erythropoiesis. Immunosuppressive therapy with cyclosporin A (6.25 mg/kg BW orally, twice daily) and prednisolone (initially 5 mg/kg BW intravenously, twice daily) from the 9th day on led to a distinct regeneration of erythropoiesis with reticulocyte counts up to 126/1000 (341.000/microliter) and normalisation of the red blood picture as well as the general state of health. The therapy with cyclosporin A was continued for five months, reducing the dosis after 30 days to 6.25 mg/kg BW orally once daily corresponding to an extremely high blood level of cyclosporine A. At control examinations 24 and 63 days after depositing therapy all parameters of the red blood picture were within the reference range. This case report indicates that pure red cell aplasia can be due to an autoimmune process in cats also as well.

Haematological disorders associated with feline retrovirus infections.

Feline oncornavirus and lentivirus infections have provided useful models to characterize the virus and host cell factors involved in a variety of marrow suppressive disorders and haematological malignancies. Exciting recent progress has been made in the characterization of the viral genotypic features involved in FeLV-associated diseases. Molecular studies have clearly defined the causal role of variant FeLV env gene determinants in two disorders: the T-lymphocyte cytopathicity and the clinical acute immunosuppression induced by the FeLV-FAIDS variant and the pure red cell aplasia induced by FeLV-C/Sarma. Variant or enFeLV env sequences also appear to play a role in FeLV-associated lymphomas. Additional studies are required to determine the host cell processes that are perturbed by these variant env gene products. In the case of the FeLV-FAIDS variant, the aberrant env gene products appear to impair superinfection interference, resulting in accumulation of unintegrated viral DNA and cell death. In other cases it is likely that the viral env proteins interact with host products that are important in cell viability and/or proliferation. Understanding of these mechanisms will therefore provide insights to factors involved in normal lymphohaematopoiesis. Similarly, studies of FeLV-induced haematological neoplasms should reveal recombination or rearrangement events involving as yet unidentified host gene sequences that encode products involved in normal cell growth regulation. These sequences may include novel protoncogenes or sequences homologous to genes implicated in human haematological malignancies. The haematological consequences of FIV are quite similar to those associated with HIV. As with HIV, FIV does not appear to directly infect myeloid or erythroid precursors, and the mechanisms of marrow suppression likely involve virus, viral antigen, and/or infected accessory cells in the marrow microenvironment. Studies using in vitro experimental models are required to define the effects of each of these microenvironmental elements on haematopoietic progenitors. As little is known about the molecular mechanisms of FIV pathogenesis, additional studies of disease-inducing FIV strains are needed to identify the genotypic features that correlate with virulent phenotypic features. Finally, experimental FIV infection in cats provides the opportunity to correlate in vivo virological and haematological changes with in vitro observations in a large animal model that closely mimics HIV infection in man.