Thalidomide (Thal) and its derivatives, Lenalidomide (Len) and Pomalidomide (POM), are immune
modulatory drugs (IMiDs) used in the treatment of multiple myeloma (MM) and few other
hematological malignancies. Although they represent the backbone treatment for both newly
diagnosed and relapse/refractory MM patients, their clinical use remains mostly empirical because of
lack of suitable in vivo model systems to study their complex mechanisms of action. Murine cells are
intrinsically resistant to IMiDs because of different amino acid sequence in the IMiD binding domain of
cereblon (CRBN). By building upon our extensively validated Vk*MYC transgenic mouse model of
MM, we have generated a novel transgenic mouse, Vk*MYChCRBN, expressing the full human CRBN
(hCRBN) gene under the control of its endogenous regulatory elements, rendering it IMiD sensitive.
As previously done for the Vk*MYC model, we will extensively characterize the new Vk*MYChCRBN
model and will use it to understand the IMiD effects on the tumor and the immune system with the
ultimate goal to inform clinical practice.