Intriguingly, in a murine model a combination of deficiencies for both HLA-II and CD4+ T cells completely abrogates the emergence of MPNs, thus suggesting that the presence of “unprimed” CD4+ T lymphocytes (retaining an active pro-inflammatory “effector phenotype”, but without specific cytotoxic abilities against MPN-mutated cells) may be required for the emergence of an “MPN-permissive” TME [107]. The gene discussed is CD4; the disease is myeloproliferative disorder.