T-cell pseudolymphoma secondary to ixazomib for multiple myeloma.

We present a case of a 54-year-old male with multiple myeloma (MM) who presented with widespread pruritic erythematous lesions following ixazomib treatment. This occurred after his third cycle of treatment with ixazomib, thalidomide and dexamethasone and was controlled by potent steroids and temporary cessation of ixazomib. The strong correlation between the timeline of the rash, ixazomib treatment and subsequent cessation led to a diagnosis of a drug-induced rash. Skin biopsy histology, immunochemistry and the absence of monoclonal T-cell receptor gene rearrangement further confirmed the diagnosis of a T-cell pseudolymphoma secondary to ixazomib. Ixazomib is an oral proteasome inhibitor used in the treatment of MM. Other proteasome inhibitors have been reported to trigger cutaneous adverse effects. However, to our knowledge, this is the first report of pseudolymphoma following proteasome inhibitor use. Dermatologists should be aware of this potential effect and the possible management pathways such as cessation and dose reduction.

Overexpression of wild-type or mutants forms of CEBPA alter normal human hematopoiesis.

CCAAT/enhancer-binding protein-α (C/EBPα/CEBPA) is mutated in approximately 8% of acute myeloid leukemia (AML) in both familial and sporadic AML and, with FLT3 and NPM1, has received most attention as a predictive marker of outcome in patients with normal karyotype disease. Mutations clustering to either the N- or C-terminal (N- and C-ter) portions of the protein have different consequences on the protein function. In familial cases, the N-ter form is inherited with patients exhibiting long latency period before the onset of overt disease, typically with the acquisition of a C-ter mutation. Despite the essential insights murine models provide the functional consequences of wild-type C/EBPα in human hematopoiesis and how different mutations are involved in AML development have received less attention. Our data underline the critical role of C/EBPα in human hematopoiesis and demonstrate that C/EBPα mutations (alone or in combination) are insufficient to convert normal human hematopoietic stem/progenitor cells into leukemic-initiating cells, although individually each altered normal hematopoiesis. It provides the first insight into the effects of N- and C-ter mutations acting alone and to the combined effects of N/C double mutants. Our results mimicked closely what happens in CEBPA mutated patients.