LIN28B is essential for human fetal B-lymphopoiesis and initiation of KMT2A::AFF1 infant leukemia.

LIN28B is crucial for human fetal B-lymphopoiesis and drives the initiation of KMT2A::AFF1 infant leukemia, with knockout preventing leukemic transformation.

• Why it matters: Understanding the molecular basis of infant ALL, especially its initiation in utero and aggressive nature, is vital for developing targeted therapies, as current treatments have poor outcomes.
• What they did: The study compared fetal and adult hematopoietic stem/progenitor cell transcriptomes, identified LIN28B as a fetal-specific oncogene, and used CRISPR-Cas9 models to assess its role in leukemogenesis.
• The result: LIN28B was found essential for fetal B-lymphopoiesis and necessary for KMT2A::AFF1-driven leukemia initiation, suggesting it as a promising therapeutic target for aggressive infant leukemias.