Cyclic hematopoiesis in a mixed-breed dog: case report and brief review

Abstract

An 8-wk-old, male, mixed-breed puppy was adopted from a rescue organization. From the time of adoption, the puppy suffered episodes of illness affecting various organ systems, which resolved with supportive therapy but relapsed once medical therapy was discontinued. Review of the hematologic data revealed cyclic fluctuations in circulating blood cells. Cyclicity was most prominent in neutrophils, with recurrent severe neutropenia. Neutropenic episodes lasted 5-6 d, with regular cycles of 11-14 d between nadir neutrophil counts. Genetic testing determined that the patient was homozygous mutant for the frameshift mutation in the adaptor protein complex 3 β-subunit (AP3B1) gene, originally identified in gray collies with cyclic hematopoiesis (CH). Pedigree information was not available, but the patient's features were phenotypically distinct from those of collies. We describe here a case of the AP3B1 mutation in a mixed-breed dog that did not resemble a collie, undescribed previously, to our knowledge. Our findings indicate that the AP3B1 mutation and CH are present within the general canine population and are not restricted to collies.

Keywords: bone marrow; canine diseases; cyclic hematopoiesis; genetic diseases; hematology; neutropenia; veterinary pathology.

Figures 1–4.

Cyclic hematopoiesis (CH) in a mixed-breed dog. Figure 1. Neutrophil count over 150 d prior to the diagnosis of CH in a mixed-breed puppy. The neutrophil count fluctuated, with regular cycles of 11–14 d resulting in severe neutropenia. The blue shaded area indicates the neutrophil count RI. The red arrows are all of the same size and represent a period of ~12 d. Figure 2. Humeral bone marrow core biopsy collected during a neutropenic episode, with marked paucity of granulocytic precursors (thick arrow). Erythrocytic (thin arrows, and most nucleated cells present) and megakaryocytic precursor (arrowhead) frequency and morphology are unremarkable. The myeloid:erythroid ratio is markedly decreased. H&E. Figure 3. The puppy does not have phenotypic features suggestive of a collie and is presumed to be a cross between a Labrador Retriever and a Mastiff. Coat color is gray, brown, and white, suggestive of hypopigmentation. The color of the nose and rims of the eyes is also gray rather than black, supporting hypopigmentation. Figure 4. Peroxidase cytograms from an Advia 2120i hematology analyzer (Siemens); puppy with CH (left) and a hematologically unremarkable dog (right). The neutrophils from the affected dog have decreased peroxidase content, demonstrated by a shift to the left. This resulted in neutrophils, which are normally found in gate D, being counted mainly as monocytes (gate C) by the analyzer. The x-axis represents peroxidase content; the y-axis represents cell size. Gates: A = lymphocytes, B = large unstained cells, C = monocytes, D = neutrophils, and E = eosinophils.