**3. Current knowledge of the etiology and predisposing factors of MM in companion animals**

Factors associated with the development of MM in companion animals have not been identified. In human patients, exposure to high doses of ionizing radiation has been linked to MM development according to some studies [38-40]. In relation to x-rays, the results of many cohort studies in human beings have been inconsistent, in some cases suggesting that frequent exposure has a negligible effect and in other that it is a signifi‐ cant risk [41-43]. In one report of equine MM, one horse was used regularly for teaching radiology and Pusterla et al. [3] suggested that it might exists an association between ex‐ posure to x-rays and neoplastic transformation.

Genetic and hereditary factors may also play a role in MM development [44-45]. Recurrent infections or antigen stimulation have been proposed as predisposing factors, although epi‐ demiological studies have not been confirmed this association [46]. Infections with several virus diseases in human patients appear related to an elevated MM risk, although some data do not support a potentially causal relationship between these infections and MM [46-50]. In cats, a link between MM and virus such as feline leukemia virus (FeLV) and feline immuno‐ deficiency virus (FIV) has not been identified, but a diagnosis of the disease among sibling suggests a familiar association [29]. The role of oncogenes, tumor-suppresor genes, cyto‐ kines, and their interaction with the bone marrow environment in the etiopathogenesis of the MM are currently being investigated in animal models. Overexpression of cell cycle reg‐ ulators, such as cyslin D1 and disregulation of receptor tyrosine kinase have been implicated in the pathogenesis of plasma cell tumors and MM [51]. Progression of B cell lymphoma to MM and of solitary plasma cell tumors to MM in dogs and cats have been reported [52-53].
