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<p>Emergence of <i>BCR::ABL1</i> 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 <i>FLT3</i>-internal tandem duplication (<i>FLT3-</i>ITD) and <i>BCR::ABL1</i> were absent, while targeted sequencing identified an <i>FBXW7</i> mutation. After induction failure, he underwent allo-HSCT. At post-transplant relapse during venetoclax plus azacitidine maintenance, <i>FLT3-</i>ITD and <i>WT1</i> mutations newly emerged. Quizartinib induced remission, but a second relapse occurred with emergence of <i>BCR::ABL1</i> while <i>FLT3-</i>ITD persisted. Cytogenetics showed t(9;22)(q34;q11), and FISH confirmed <i>BCR::ABL1</i> fusion in 73% of bone marrow cells, with the minor transcript (p190) confirmed by quantitative PCR. Despite no <i>ABL1</i> kinase domain mutations, imatinib and ponatinib failed to control the disease. These findings suggest that <i>BCR::ABL1</i> emergence may represent a bypass resistance mechanism arising under quizartinib-associated selective pressure.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Hidetoshi Irifune,
  • Yuichiro Semba,
  • Yasufumi Uehara,
  • Takanori Ohta,
  • Yasuhiro Sugio,
  • Koichi Akashi,
  • Takahiro Maeda,
  • Yuju Ohno

摘要

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.