This case highlights the value of genetic testing and identifies <i>DUSP22-IRF4-</i>associated ALCL in the setting of HIV-associated lymphoproliferative disorders.
These findings identify a novel recurrent <i>MSC</i> mutation as a key driver of the CD30-IRF4-MYC axis and cell cycle progression in a unique subset of ALCLs.
Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK<sup>+</sup> and ALK<sup>-</sup> anaplastic large cell lymphoma (ALCL).
Overall, these results show that IRF4 is involved in STAT3-oncogenic signaling and its inhibition provides alternative avenues for the design of novel/combination therapies of ALCL.
<b>Results:</b> IRF4/MUM1 expression was observed in 33% of all patients (23/69), most frequently in patients with anaplastic large cell lymphoma (ALCL, 78%, 7/9).
Collectively, our results demonstrate that ALCLs are dependent on IRF4 and MYC signaling and that MYC may represent a promising target for future therapies.
By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas.
Among all cutaneous T-cell lymphoproliferative disorders, FISH for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%, respectively (P=0.00002, Fisher's exact test).
Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases.