[FLT3-ITD mutation-positive acute myeloid leukemia undergoing clonal transition with PTPN11 mutation at relapse]

Rinsho Ketsueki. 2024;65(2):63-68. doi: 10.11406/rinketsu.65.63.
[Article in Japanese]

Abstract

A 28-year-old man was diagnosed with acute myelomonocytic leukemia. He achieved complete remission (CR) after two cycles of induction therapy. However, after consolidation therapy, bone marrow aspiration performed to prepare for allogeneic hematopoietic stem cell transplantation revealed disease relapse. Companion diagnostics confirmed the presence of the FLT3-ITD mutation. The patient received gilteritinib monotherapy and achieved CR. Subsequently, he underwent unrelated allogeneic bone marrow transplantation. One year after transplantation, the patient relapsed, and gilteritinib was resumed. However, the leukemia progressed, and panel sequencing using a next-generation sequencer showed that the FLT3-ITD mutation disappeared. A mutation in PTPN11, which regulates the RAS/MAPK signaling pathway, was also detected. Gilteritinib was discontinued, and the patient achieved CR with salvage chemotherapy. He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.

Keywords: Acute myeloid leukemia; Clonal transition; FMS-like tyrosine kinase 3 (FLT3); Protein tyrosine phosphatase non-receptor type 11 (PTPN11).

Publication types

  • Case Reports
  • English Abstract

MeSH terms

  • Adult
  • Aniline Compounds
  • Chronic Disease
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Mutation
  • Pathologic Complete Response
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Pyrazines
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • gilteritinib
  • Aniline Compounds
  • Pyrazines
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11