Multiple Lineage Switches in a Pediatric Case With a KMT2A::AFF1-Positive Acute Lymphoblastic Leukemia: How Cell Plasticity Induces Immunotherapy Failure.

We report a case of multiple lineage switches (rare events mostly occurring in infants) in a 10-year-old female with KMT2A::AFF1-positive acute lymphoblastic leukemia (ALL). Although she underwent standard chemotherapy, immunotherapy, and hematopoietic stem cell transplantation, the leukemic clone continuously switched on acute myeloid leukemia (AML) or ALL and maintained immunoglobulin/T-cell receptor rearrangements in addition to showing a high therapy-escaping grade. As other genes are involved in this event, and after considering the selective pressure imposed by the applied treatment, characterizing the cell-of-origin that is capable of proliferating toward both lineages while attempting to design targeted therapies is mandatory.