Activation of the Shh pathway in multiple myeloma cell lines NCI-H929 and KMS12 stimulates the self-renewal and expansion of CD138+CD19− CSCs; whereas inhibition of the Shh pathway by cyclopamine or by the Shh neutralizing antibody 5E1 decreases the clonal capacity of multiple myeloma cell lines and CD138− cells through the induction of plasma differentiation (121). Here, SHH is linked to plasma cell myeloma.