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  • Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma.

Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma.

Proceedings of the National Academy of Sciences of the United States of America (2014-10-25)
Dongmei Yang, Wuguo Chen, Jie Xiong, Carly J Sherrod, David H Henry, Dirk P Dittmer
ABSTRACT

Primary effusion lymphoma (PEL) is an AIDS-defining cancer. All PELs carry Kaposi sarcoma-associated herpesvirus (KSHV). X chromosome-targeted sequencing of PEL identified 34 common missense mutations in 100% of cases. This included a Phe196Ser change in the interleukin 1 receptor-associated kinase 1 (IRAK1). The mutation was verified in primary PEL exudates. IRAK1 is the binding partner of MyD88, which is mutated in a fraction of Waldenström macroglobulinemia. Together, these two mediate toll-like receptor (TLR) signaling. IRAK1 was constitutively phosphorylated in PEL and required for survival, implicating IRAK1 and TLR signaling as a driver pathway in PEL and as a new drug development target.

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