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

[primary effusion lymphoma]

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 Phe 196 S er change in the interleukin 1 receptor-associated kinase 1 (IRAK 1 ). The mutation was verified in primary PEL exudates . IRAK 1 is the binding partner of MyD 88 , which is mutated in a fraction of Waldenström macroglobulinemia . Together , these two mediate toll-like receptor (TLR ) signaling . IRAK 1 was constitutively phosphorylated in PEL and required for survival , implicating IRAK 1 and TLR signaling as a driver pathway in PEL and as a new drug development target .