Abstract
Background/Objectives: Relapsed acute myeloid leukemia (AML) is often characterized by clonal evolution and acquired genomic abnormalities, which can inform prognosis and direct therapeutic decisions. The emergence of high-risk chromosomal rearrangements during relapse is of particular significance, yet the impact of rare and complex events remains poorly understood. This report details a case of relapsed AML that demonstrated rare MYC and MECOM rearrangements and additional features that were not observed at initial diagnosis, emphasizing the clinical relevance of serial cytogenetic assessments. Case Description: A 70-year-old man was initially diagnosed with AML, exhibiting monocytic differentiation, an 11q23 deletion involving KMT2A loss, and a U2AF1 mutation. After achieving remission with azacitidine and venetoclax, the patient relapsed within ten months, necessitating reevaluation and modification of therapy. Repeat cytogenetic analysis at relapse revealed a distinct t(3;8)(q26.2;q24.3) exhibiting MYC and MECOM rearrangements, features that were absent at initial diagnosis. Conclusions: This case underscores the importance of serial cytogenetic and molecular profiling in relapsed AML. The emergence of new abnormalities upon relapse suggested underlying genomic instability and clonal evolution. MYC rearrangements are notably rare in AML, especially with concurrent MECOM rearrangements, highlighting a unique feature of this case. The identification of novel abnormalities at relapse may carry prognostic and therapeutic significance and may be used to refine risk stratification. Thus, ongoing cytogenetic monitoring is essential to adapt management approaches in evolving disease contexts.