This study highlights a case of MPN with a more clinically aggressive Type 1 calreticulin (<i>CALR</i>) mutation, where a combination of low-dose IL-2 immunotherapy and targeted therapy with oral tretinoin (all-trans retinoic acid, ATRA, a vitamin A derivative) improved immune cells, particularly NK-cell-mediated destruction of malignant cells, reduced <i>CALR</i> mutation levels to undetectable, and alleviated disease symptoms. The gene discussed is IL2; the disease is myeloproliferative neoplasm.