Acute myeloid leukemia with isocitrate dehydrogenase-2 (IDH2) mutation

Acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation is an aggressive hematologic malignancy characterized by the clonal proliferation and accumulation of immature myeloid precursors within the bone marrow and peripheral blood, occurring primarily in adult populations

Acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation is an aggressive hematologic malignancy characterized by the clonal proliferation and accumulation of immature myeloid precursors within the bone marrow and peripheral blood, occurring primarily in adult populations Clinically, this leads to bone marrow failure typically manifesting with severe cytopenias, such as anemia, neutropenia, and thrombocytopenia, alongside elevated risks of infection, hemorrhage, and systemic fat...

Pathophysiologically, somatic mutations in the mitochondrial *IDH2* gene confer neomorphic enzyme activity, driving the aberrant reduction of alpha-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG) The abnormal accumulation of 2-HG inhibits alpha-ketoglutarate–dependent epigenetic regulators, causing genome-wide DNA and histone hypermethylation that arrests normal myeloid hematopoietic differentiation

Pathophysiologically, somatic mutations in the mitochondrial *IDH2* gene confer neomorphic enzyme activity, driving the aberrant reduction of alpha-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG) The abnormal accumulation of 2-HG inhibits alpha-ketoglutarate–dependent epigenetic regulators, causing genome-wide DNA and histone hypermethylation that arrests normal myeloid hematopoietic differentiation

Clinically, this leads to bone marrow failure typically manifesting with severe cytopenias, such as anemia, neutropenia, and thrombocytopenia, alongside elevated risks of infection, hemorrhage, and systemic fatigue