No abstract

Key Points Genome editing of primary human HSPCs generates MLL leukemias that model clinical disease features and molecular pathogenesis.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated immune activation.  Primary HLH involves hereditary deficits in cytotoxic lymphocytes while secondary HLH is triggered by extrinsic factors. The HLH‐2004 criteria are widely used for clinical diagnosis, yet their specificity for HLH or their ability to differentiate primary from secondary disease is unclear, potentially leading to inappropriate treatment. We describe several cases where fulfillment of HLH‐2004 criteria obscured the diagnoses of underlying malignancies and delayed curative management. These issues are remedied without waiting for genetic testing results through an alternative diagnostic approach using flow cytometry–based immunologic assays and a thorough investigation for malignancy.

Key Points• Genome editing induces t(9;11) chromosomal translocations and transforms primary CD34 1 human cord blood cells leading to acute leukemia.• CD9 is upregulated in primary t(9;11) cells and is a useful marker for enrichment of genome-edited MLLrearranged cells in vitro.