Canine Cyclic Neutropenia

Cyclic hematopoiesis. Effects of endotoxin on colony-forming cells and colony-stimulating activity in grey collie dogs.

“…The cycle length for reticulocytes, platelets, neutrophils, monocytes, and lymphocytes is precisely the same but the pattern of cyclic variation for each cell line is different, implicating the pluripotent stem cell as the site of the defect in this disease (3). Marrow transplantation studies have shown that the disorder can be eliminated by total body irradiation and bone marrow transplantation from a normal dog (6), and that the blood cycling can be produced in previously normal dogs by irradiation and infusion of grey collie marrow cells (7). Therefore, alteration ofthe intrinsic regulation of the stem cell pool or pools is thought to produce this autosomal recessive disease (4,8,9).…”

Canine cyclic hematopoiesis is associated with abnormal purine and pyrimidine metabolism.

“…Studies of granulocytic and erythroid precursor cells have shown fluctuations in these committed progenitor cell populations over the cycle of cell counts but have not explained the mechanism(s) causing cyclic hematopoiesis (7)(8)(9)(10)(11). Bone marrow transplantation experiments have shown that this disease can be cured or transferred to a normal littermate by irradiation and marrow cell infusion, clearly implicating the marrow stem cell pool(s) as the site of the defect (12)(13)(14). Recently we have demonstrated that lithium carbonate eliminates the severe recurrent neutropenia, smooths the fluctuations of other cell counts, and eliminates the marked cycling of neutrophilic colony-forming cells in these dogs (15,16).…”

The inhibitory effect of circulating lymphocytes on granulopoiesis in human cyclic neutropenia in vitro.

“…The mechanism of cyclic hematopoiesis in gray collie dogs has been studied extensively, and it is generally accepted that the disorder is the result of periodic pluripotential stem cell failure (Pact et al 1973 ;Weiden et al 1974). Recently Krance and coworkers (1982) reported a patient who acquired CN from her histocompatible sibling donor following bone marrow transplantation as treatment for acute lymphoblastic leukemia.…”

“…The cause of cycling has been shown to be fluctuating production of cells by the bone marrow in both humans and dogs (Dale et al 1972a, b ;Guerry et al 1973;Patt et al 1973;Meuret and Fliedner 1974). In gray collie dogs, a congenital disorder of the pluripotential stem cells has been confirmed by bone marrow transplantation (Dale and Graw 1974;Weiden et al 1974;Jones et al 1975), and cyclic production of all blood elements has been shown in the animal (Dale et al 1972b;Weiden et al 1974). In human, however, the exact etiology of CN remained unclear and this condition, which appears to be acquired in some individuals and congenital in others, may occur by several pathogenic mechanisms (Wright et al 1981).…”