Myelofibrosis (myeloid metaplasia, myelosclerosis) is a disorder of bone where the marrow is replaced by scar (fibrous) tissue, due to a proliferative response by bone-marrow fibroblasts.
Myelofibrosis has been classified in human medicine as either primary or secondary depending on the underlying etiology, but only secondary myelofibrosis has been reported in the dog.
Causes of myelofibrosis in dogs include, in order of importance:
- Long-term drug exposure - phenobarbital, phenytoin, phenylbutazone and colchicine
- Immune-mediated hemolytic anemia
- Neoplasia - leukemia, lymphoma, mammary tumors, multiple myeloma, malignant histiocytosis, gastrinoma, mast cell tumor
- Systemic inflammatory diseases - pyometra, pancreatitis, hepatitis, glomerulonephritis
- Immune-mediated thrombocytopenia
- Pyruvate kinase deficiency
- Myelodysplasia syndrome
- Breed predisposition - severe nonregenerative macrocytic hypochromic anemia in pregnant female Beagles
- Whole body γ-radiation
Diagnosis requires multiple bone marrow core biopsies and histological examination of other organ tissue samples, confirming the increased presence of fibrosis within bone marrow spaces and increased extramedullary hematopoiesis in other organs such as the liver and spleen.
In severely anemic dogs, whole blood transfusions of fresh frozen plasma may be required as a palliative strategy to forestall a demise.
Development of new protein kinase inhibitors has shown promise at treating myelofibrosis secondary to lymphoma.
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- William AD et al (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[18.104.22.168(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem 54(13):4638-4658