[Update on acute leukemia of ambiguous lineage in 2023 - Recommendations of the French Society for Childhood and Adolescent Cancer and Leukemia (SFCE)].

Acute leukemias of ambiguous lineage (ALAL) represent between 3 and 5% of childhood AL. This term encompasses many subtypes of AL that have been defined according to the immunophenotypic profile based on the expression of various lineage markers. This classification has been modified and enriched during the last decade thanks to the improvement of molecular biology techniques, which have led to reconsider the ontogenic proximity existing between certain forms of ALAL. This increasing diagnostic complexity justifies the establishment of a close communication between clinicians and biologists in the management of these rare forms of AL. Indeed, the initial classification remains the cornerstone of their management since it conditions the future choice of therapeutic protocol. Thus, with the notable exception of undifferentiated forms of AL or AUL (for acute undetermined leukemia), it is now accepted that ALAL benefit from a lymphoid-based therapy approach. As with the management of "classic" acute lymphoblastic leukemias (ALL), the evaluation of response to treatment will determine the modalities of therapeutic intensification. The objective of improving the prognosis of ALAL justifies, in the long term, their future inclusion in the international ALLTogether protocol while continuing in-depth molecular exploration of these patients to identify targeted therapies.