B-cell precursor acute lymphoblastic leukaemia with IGH::CEBP rearrangement: what have we learnt over the years?

B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is a haematologic malignancy marked by the rapid proliferation of immature B cells in the bone marrow. While BCP-ALL most commonly affects children aged 1-5 years, it remains the most prevalent subtype of ALL in adolescence and adulthood. Chromosomal translocations involving the immunoglobulin ( IG ) locus and partner genes are proven useful for risk stratification and guiding clinical trials for therapeutic decision. This includes translocations with CCAAT/enhancer-binding proteins (CEBP) , which are particularly rare. This rarity has limited efforts to characterise their genetic and clinical profiles, making risk stratification for IGH::CEBP -rearranged BCP-ALL challenging. In this letter, we review the clinical and demographic characteristics of all reported IGH::CEBP cases prior to 2024 and introduce new cases, with preliminary analysis to encourage further investigation into this poorly understood subtype. This study delivers new insights into the molecular and cytogenetic landscape of IGH::CEBP rearrangements in BCP-ALL, and lays a foundation for further investigation into CEBP family roles in haematopoietic development and leukemogenesis, especially in the context of Down syndrome. Finally, it introduces the ongoing international collaborative effort to assemble the largest known IGH::CEBP cohort for comprehensive risk stratification and prognostic evaluation.