Lineage switch in a pediatric patient with KMT2A-MLLT3 from acute megakaryoblastic leukemia to T cell acute lymphoblastic leukemia at the fourth relapse after allo-HSCT: with literature review

Int J Hematol. 2023 May;117(5):781-785. doi: 10.1007/s12185-022-03504-8. Epub 2022 Dec 6.

Abstract

We present a patient with acute megakaryoblastic leukemia (AMKL) harboring KMT2A-MLLT3 that converted to T cell acute lymphoblastic leukemia (T-ALL) at her fourth relapse. A 4-year-old girl developed AMKL with multiple swollen lymph nodes. She exhibited several recurrences in the bone marrow and died of septic shock after her fourth relapse. Bone marrow cells at the initial diagnosis and at all four relapses had the same KMT2A-MLLT3 fusion transcript. She also developed a somatic mutation (c.7177C > T p.Q2393X) of NOTCH1 at the fourth relapse. This sequential phenotypic and cytogenetic study may yield valuable insights into the mechanism of AMKL to T-ALL lineage switch and possible implications for treatment selection.

Keywords: Acute megakaryoblastic leukemia; KMT2A-MLLT3; Lineage switch; Relapse; T cell acute lymphoblastic leukemia.

Publication types

  • Review
  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Megakaryoblastic, Acute* / genetics
  • Leukemia, Megakaryoblastic, Acute* / therapy
  • Nuclear Proteins / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Recurrence
  • T-Lymphocytes

Substances

  • MLLT3 protein, human
  • Nuclear Proteins
  • KMT2A protein, human