In this week's episode, we'll learn about how TET2 is often mutated in myeloid malignancies and clonal hematopoiesis. In new work, expansion of Tet2-mutant HSPCs was dependent on Ncoa4, the cargo receptor mediating ferritinophagy. We’ll iron out the implications. After that: a double-oh-seven license to kill in T-cell leukemia/lymphoma. WU-CART-007 is an off-the-shelf CAR T product with manageable safety and encouraging efficacy. With further work, it could become a new option for patients in urgent need of therapy. Finally: a comprehensive genetic study of classical Hodgkin lymphoma using circulating tumor DNA. This new research provides novel and complex insights on genetic subtypes, prognostic biomarkers, neoantigens in the disease environment, and more.

Featured Articles:

• An in vivo barcoded CRISPR-Cas9 screen identifies Ncoa4-mediated ferritinophagy as a dependence in Tet2-deficient hematopoiesis
• Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for patients with relapsed/refractory T-cell malignancies
• A comprehensive genetic study of classic Hodgkin lymphoma using circulating tumor DNA

In this week's episode we'll learn about targeting NPM1 in acute myeloid leukemia. Researchers report the first clinical evidence of a menin inhibitor inducing complete remissions in AML with a NPM1 mutation. This validates NPM1 as a new therapeutic target in AML, alongside FLT3, IDH1/2, and KMT2A. Also on the podcast: targeting CD137 to prevent graft-versus-host disease. In nonhuman primates, a single dose of a CD137 antibody-drug conjugate provided long-term protection, with one important caveat: the potential for viral reactivation.

Featured Articles:

• Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study
• A single dose of a CD137 antibody–drug conjugate protects rhesus macaque allogeneic HCT recipients against acute GVHD

Blood Editor, Dr. Thomas Coates interviews Dr. Emanuele Angelucci on his paper, "How I manage iron overload in the hematopoietic cell transplantation setting" which is featured in Blood's "How I Treat Series on Iron Overload in Hematologic Disorders".

See the full How I Treat series in volume 145 issue 4 of Blood.