Skip to content
DraconiticResearch
Search Sources API
189,105 studies31 sourcesUpdated 40 min ago
Peer-reviewedCC BY-NC-ND 4.0Annals of Hematology

Sequential emergence of FLT3-ITD and BCR::ABL1 during disease progression in relapsed acute myeloid leukemia

  • Hidetoshi Irifune1
  • Yuichiro Semba2,3
  • Yasufumi Uehara1
  • Takanori Ohta1
  • Yasuhiro Sugio1
  • Koichi Akashi2
  • Takahiro Maeda3
  • Yuju Ohno1
  1. 1Department of Hematology, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-ku, Kitakyushu-shi, Fukuoka 802-8561 Japan
  2. 2Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  3. 3Division of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Read full textPDFDOICite

Abstract

Emergence of BCR::ABL1 during FMS-like tyrosine kinase 3 (FLT3) inhibitor therapy is a rare resistance mechanism in acute myeloid leukemia (AML). We report a case of relapsed AML with sequential clonal evolution after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A previously healthy man in his 30s was diagnosed with AML with maturation; initial cytogenetics were normal, and both FLT3-internal tandem duplication (FLT3-ITD) and BCR::ABL1 were absent, while targeted sequencing identified an FBXW7 mutation. After induction failure, he underwent allo-HSCT. At post-transplant relapse during venetoclax plus azacitidine maintenance, FLT3-ITD and WT1 mutations newly emerged. Quizartinib induced remission, but a second relapse occurred with emergence of BCR::ABL1 while FLT3-ITD persisted. Cytogenetics showed t(9;22)(q34;q11), and FISH confirmed BCR::ABL1 fusion in 73% of bone marrow cells, with the minor transcript (p190) confirmed by quantitative PCR. Despite no ABL1 kinase domain mutations, imatinib and ponatinib failed to control the disease. These findings suggest that BCR::ABL1 emergence may represent a bypass resistance mechanism arising under quizartinib-associated selective pressure.

Related

  1. Purpureocillium lilacinum Fungemia Masquerading as an Unidentified Yeast in a Heavily Immunosuppressed Patient With Relapsed Multiple Myeloma and Therapy-Related Mixed-Phenotype Acute Leukemia: A Case Report
    Mostafa M Abouzahra, Enas Abdallah, Carolyn K Lackore +2
    CureusPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  2. A Multivariable Mixed-Effects Framework for Predicting Disease Progression in Acute Myeloid Leukemia Using Peripheral Hematology, FLT3 Expression, and Patient Compliance
    M. M. Amiri Dumar, M. Aghajani
    medRxivPreprintCC BYFull textGeneral medicinemedRxiv
  3. Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.
    Shisen Wang, Wenbing Liu, Ying Wang +10
    Cancer medicinePeer-reviewedCC BY-NC-NDFull textEpidemiology & public healthEurope PMC
  4. Hypofractionated Total Marrow and Lymphoid Irradiation for Relapsed/Refractory Leukemia Using Helical Tomotherapy: Workflow and Dosimetric Analysis
    Wenjie Ni, Xiunan Wang, Hui Yang +5
    Yonsei Medical JournalPeer-reviewedCC BY-NC 4.0Full textOncologyPMC
  5. Addition of thiotepa to total body irradiation-based conditioning in allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute leukemia and lymphoma: a propensity score-matched retrospective study.
    Minglu Li, Shuqin Zhang, Xiaoyong Man +4
    Annals of hematologyPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMCDOAJ

Cite

BibTeXRIS
BibTeX
@article{irifune2026sequential,
  title = {{Sequential emergence of FLT3-ITD and BCR::ABL1 during disease progression in relapsed acute myeloid leukemia}},
  author = {Hidetoshi Irifune and Yuichiro Semba and Yasufumi Uehara and Takanori Ohta and Yasuhiro Sugio and Koichi Akashi and Takahiro Maeda and Yuju Ohno},
  journal = {Annals of Hematology},
  year = {2026},
  month = jul,
  doi = {10.1007/s00277-026-07196-6},
  url = {https://doi.org/10.1007/s00277-026-07196-6},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Sequential emergence of FLT3-ITD and BCR::ABL1 during disease progression in relapsed acute myeloid leukemia
AU  - Hidetoshi Irifune
AU  - Yuichiro Semba
AU  - Yasufumi Uehara
AU  - Takanori Ohta
AU  - Yasuhiro Sugio
AU  - Koichi Akashi
AU  - Takahiro Maeda
AU  - Yuju Ohno
PY  - 2026
DA  - 2026/07/28
JO  - Annals of Hematology
DO  - 10.1007/s00277-026-07196-6
UR  - https://doi.org/10.1007/s00277-026-07196-6
AB  - Emergence of BCR::ABL1 during FMS-like tyrosine kinase 3 (FLT3) inhibitor therapy is a rare resistance mechanism in acute myeloid leukemia (AML). We report a case of relapsed AML with sequential clonal evolution after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A previously healthy man in his 30s was diagnosed with AML with maturation; initial cytogenetics were normal, and both FLT3-internal tandem duplication (FLT3-ITD) and BCR::ABL1 were absent, while targeted sequencing identified an FBXW7 mutation. After induction failure, he underwent allo-HSCT. At post-transplant relapse during venetoclax plus azacitidine maintenance, FLT3-ITD and WT1 mutations newly emerged. Quizartinib induced remission, but a second relapse occurred with emergence of BCR::ABL1 while FLT3-ITD persisted. Cytogenetics showed t(9;22)(q34;q11), and FISH confirmed BCR::ABL1 fusion in 73% of bone marrow cells, with the minor transcript (p190) confirmed by quantitative PCR. Despite no ABL1 kinase domain mutations, imatinib and ponatinib failed to control the disease. These findings suggest that BCR::ABL1 emergence may represent a bypass resistance mechanism arising under quizartinib-associated selective pressure.
SN  - 0939-5555
SN  - 1432-0584
ER  -