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

Pediatr Blood Cancer. 2025 Oct;72(10):e31950. doi: 10.1002/pbc.31950. Epub 2025 Aug 1.

Abstract

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.

Keywords: KMT2A/MLL rearrangements; acute lymphoblastic leukemia; acute myeloid leukemia; children; lineage switch.

Publication types

  • Case Reports

MeSH terms

  • Cell Lineage*
  • Child
  • DNA-Binding Proteins
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Histone-Lysine N-Methyltransferase* / genetics
  • Histone-Lysine N-Methyltransferase* / metabolism
  • Humans
  • Immunotherapy*
  • Myeloid-Lymphoid Leukemia Protein* / genetics
  • Myeloid-Lymphoid Leukemia Protein* / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Transcriptional Elongation Factors* / metabolism

Substances

  • Histone-Lysine N-Methyltransferase
  • Myeloid-Lymphoid Leukemia Protein
  • KMT2A protein, human
  • AFF1 protein, human
  • Transcriptional Elongation Factors
  • DNA-Binding Proteins