Identification of acute myeloid leukemia in dogs using flow cytometry with myeloperoxidase, MAC387, and a canine neutrophil‐specific antibody

Villiers, Elizabeth; Baines, Stephen; Law, Anne-Marie; Mallows, Victoria

doi:10.1111/j.1939-165x.2006.tb00089.x

Cited by 47 publications

(52 citation statements)

References 21 publications

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“…Although the morphological changes in the peripheral blood were quite similar to those of previous reports [3,11], the bone marrow findings were not characteristic of M4. Most of the blast cells had a small number of distinct magenta (azurophilic) granules in the cytoplasm, and monoblast-like cells comprised only 2.2% in the bone marrow.…”

supporting

confidence: 85%

“…The definitive diagnosis of M4 is made when myeloblasts and monoblasts together constitute more than 30% of all nucleated cells in the bone marrow, and differentiated granulocytes and monocytes each comprise more than 20% of all nucleated cells. Cases of this type of leukemia have been reported, but the hematological findings, blast cell characteristics, and clinical course of the disease have been unclear [1,2,11]. This report describes a dog diagnosed with M4 on the basis of hematological and cytochemical findings, and the clinical course during treatment with several chemotherapeutic agents and induction therapy using vitamin K 2 .…”

mentioning

confidence: 96%

“…This cytochemical staining is able to demonstrate this characteristic property of blasts in canine M4 because the pathogenesis of M4 is the differentiation of blasts to myeloid and monocytic cells. Furthermore, Villiers et al reported that when the immunophenotype of a case with M4 was analyzed by using flow cytometry, staining with several antibodies including MPO, MAC387, CD11a, CD11b, and CD11c was positive [11]. Probably, analysis of the immunophenotype using these antibodies is helpful to establish a definitive diagnosis of canine M4 more certainly.…”

mentioning

confidence: 99%

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A Dog with Acute Myelomonocytic Leukemia

Hisasue

Nishimura

Neo

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. A three-year-old dog with marked leukocytosis, lymphadenopathy, and diarrhea showed an increase in unidentified blasts in the peripheral blood, and they were proliferated in the bone marrow. The dog was diagnosed with myelomonocytic leukemia (M4) because the blast cells were demonstrated by cytochemical staining to be both myeloid and monocytic cells. Although the dog was treated with a multi-combination chemotherapy and induction therapy using vitamin K 2 , it died on day 47 after the first admission. This case is the first report of M4 in Japan.

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confidence: 85%

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confidence: 96%

mentioning

confidence: 99%

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A Dog with Acute Myelomonocytic Leukemia

Hisasue

Nishimura

Neo

et al. 2008

The Journal of Veterinary Medical Science

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“…Although flow cytometry can be rapid and informative and may provide a very high likelihood of lymphoma and even phenotype, it is unable to provide a diagnosis of specific lymphoma subtype. 9,18,25 The practice of lymphoma diagnosis in human medicine is solidly based on histology, and this practice needs to be followed in veterinary oncology as well. Currently, most lymphoma therapy in animals is largely palliative, suggesting that collaboration is needed with oncologists to test specific protocols on single subtypes of lymphoma with a goal of therapy that is closer to curative.…”

Section: Discussionmentioning

confidence: 99%

Canine Lymphomas

et al. 2013

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Canine lymphoma is the neoplasm most often treated by chemotherapy, yet there are few data to correlate response to therapy with its different subtypes. This study is based on biopsy specimens from 992 dogs for which lymphoma was the clinical diagnosis. All cases were phenotyped by immunohistochemistry for CD3 and CD79alpha. Cases with histiocytic proliferation were evaluated immunohistochemically for CD18. Clonality was verified in 12 cases by polymerase chain reaction (PCR). Survival (event time) data and complete survival information (cause of death or time to last follow-up) were available on 456 dogs. Additional covariate information when available included size, age, sex, phenotype, stage and grade of lymphoma, mitotic index, and treatment protocol. Because of the many subtypes of B-and T-cell lymphoma, the cases were grouped into 7 diagnostic categories: (1) benign hyperplasia; (2) low-grade B-cell; (3) high-grade B-and T-cell; (4) low-grade T-cell; (5) centroblastic large B-cell of all mitotic grades (subdivided by clinical stage); (6) immunoblastic large B-cell of all mitotic grades, and (7) high-grade peripheral T-cell. Grouping was determined by histological grade (based on mitotic rate/400Â field, with low-grade 0-5, intermediate 6-10, and high-grade >10) and stage for survival function estimation. No association with survival was found for size (based on breed of dog) or sex. All diagnostic categories of indolent or low-grade type had low mitotic rates, whereas those with clinically high grades had high mitotic rates. The diagnostic category with the most cases was centroblastic large B-cell lymphoma. Compared with dogs in this largest represented group of lymphomas, dogs with high-grade lymphomas had significantly higher mortality rates, and dogs with low-grade T-cell lymphomas had significantly lower mortality rates. Treatments for high-, intermediate-, and low-grade lymphomas were divided into 4 groups: absence of treatment, chemotherapy with or without hydroxydaunorubicin, and only prednisone. Dogs with low-grade T-cell (T-zone) lymphomas had the longest median survival (622 days), whereas the shortest median survival was in dogs with T-cell high-grade (peripheral T-cell) subtype (162 days). The dogs with centroblastic large B-cell lymphomas had a median survival of 127 days with low stage, 221 days with intermediate stage, and 215 days with advanced stage. Dogs with T-zone lymphoma were probably diagnosed in later stages of disease because of the lack of signs associated with progression. As with human lymphomas, a histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of a specific subtype.

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“…These criteria have been shown to be diagnostic for TZL (Seelig et al 2014). CD34+ cases were designated as AML when associated with an expansion of CD14-positive leukocytes (Villiers et al 2006), while cases with CD5 expression were designated as ALL. Studies have not yet been performed to show that there is prognostic value to bone marrow evaluation, and since these patients were all client-owned dogs, with the full cost of all diagnostic procedures at the owners' expense, assessment of bone marrow was not included in the diagnostic process.…”

Section: Case Recruitment and Immunophenotypingmentioning

confidence: 99%

Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation

et al. 2015

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Leukemia in dogs is a heterogeneous disease with survival ranging from days to years, depending on the subtype. Strides have been made in both human and canine leukemia to improve classification and understanding of pathogenesis through immunophenotyping, yet classification and choosing appropriate therapy remains challenging. In this study, we assessed 123 cases of canine leukemia (28 ALLs, 24 AMLs, 25 B-CLLs, and 46 T-CLLs) using high-resolution oligonucleotide array comparative genomic hybridization (oaCGH) to detect DNA copy number alterations (CNAs). For the first time, such data were used to identify recurrent CNAs and inclusive genes that may be potential drivers of subtype-specific pathogenesis. We performed predictive modeling to identify CNAs that could reliably differentiate acute subtypes (ALL vs. AML) and chronic subtypes (B-CLL vs. T-CLL) and used this model to differentiate cases with up to 83.3 and 95.8 % precision, respectively, based on CNAs at only one to three genomic regions. In addition, CGH datasets for canine and human leukemia were compared to reveal evolutionarily conserved copy number changes between species, including the shared gain of HSA 21q in ALL and ∼25 Mb of shared gain of HSA 12 and loss of HSA 13q14 in CLL. These findings support the use of canine leukemia as a relevant in vivo model for human leukemia and justify the need to further explore the conserved genomic regions of interest for their clinical impact.

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Identification of acute myeloid leukemia in dogs using flow cytometry with myeloperoxidase, MAC387, and a canine neutrophil‐specific antibody

Abstract: Antigens identified by antibodies to MAC387, MPO, and NSA were expressed not just by normal mature neutrophils and monocytes, but also by neoplastic myeloblasts and monoblasts. These 3 antibodies may be useful as part of a wider panel for immunophenotyping AML in dogs.

Cited by 47 publications

References 21 publications

A Dog with Acute Myelomonocytic Leukemia

A Dog with Acute Myelomonocytic Leukemia

Canine Lymphomas

Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation

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