Secondary acquisition of BCR-ABL1 fusion in de novo GATA2-MECOM positive acute myeloid leukemia with subsequent emergence of a rare KMT2A-ASXL2 fusion

Patrick R. Blackburn, Li Huang, Andrew Dalovisio, Beth A. Pitel, Dong Chen, Jennifer L. Oliveira, Adam J. Wood, James B. Smadbeck, Sarah H. Johnson, George Vasmatzis, Claudia Haferlach, Patricia T. Greipp, Nicole L. Hoppman, Rhett P. Ketterling, Linda B. Baughn, Jess F. Peterson

Research output: Contribution to journalArticlepeer-review


Secondary acquisition of t(9;22)(q34;q11.2)/BCR-ABL1 fusion in the context of de novo acute myeloid leukemia (AML) with inv(3)(q21q26)/GATA2-MECOM rearrangement has been rarely reported. Furthermore, t(2;11)(p23;q23)/KMT2A-ASXL2 fusion has been rarely described with only a single case reported to date. We report a 45-year-old male with a diagnosis of de novo AML harboring GATA2-MECOM rearrangement in conjunction with a related subclone with concomitant inv(3) and t(9;22). The patient was treated with a tyrosine kinase inhibitor (TKI) which lead to disappearance of the inv(3)/t(9;22) subclone and subsequent expansion of the inv(3) ancestral clone. The patient was started on a 7+3 induction regimen with TKI but had persistent disease. He was placed on several additional treatment protocols and only achieved morphologic remission with a combination of fludarabine, cytarabine and filgrastim with TKI. Approximately 11.5 months after diagnosis the patient relapsed with the inv(3) clone predominating initially, followed by return of the inv(3)/t(9;22) subclone and the emergence of a second subclone with concomitant inv(3) and t(2;11)(p23;q23). Mate-pair sequencing was performed and identified a KMT2A-ASXL2 in-frame fusion, which was only recently described in a single case of therapy-related AML. For BCR-ABL1 positive AML, which generally carries a poor prognosis, treatment with TKIs has been proposed in combination with standard chemotherapy. In our case, treatment with TKI alone led to initial response of the BCR-ABL1 positive clone, but the ancestral clone quickly expanded and subsequent standard AML therapy may have led to further clonal evolution and re-emergence of the BCR-ABL1 clone in the absence of therapeutic selection.

Original languageEnglish (US)
Pages (from-to)67-71
Number of pages5
JournalCancer Genetics
StatePublished - Feb 2020


  • Acute myeloid leukemia
  • BCR-ABL1
  • Mate-pair sequencing (MPseq)
  • Next generation sequencing (NGS)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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