Case Report: High-level RUNX1/21q22 amplification is associated with multiple cytogenetic abnormalities and TP53 gene mutation in a refractory AML patient with poor clinical outcome

Background High-level amplification of RUNX1 at 21q22, commonly called iAMP21, although rare in acute myeloid leukemia (AML), is usually associated with complex cytogenetics, TP53 alterations, and poor outcomes. We present a young patient with AML and amplified 21q22 identified by FISH using a RUNX1 probe without RUNX1:RUNX1T1 fusion. Methods and case presentation A 27-year-old man whose initial complete blood count (CBC) showed pancytopenia and 16% circulating blasts on peripheral blood film was diagnosed with AML. Bone marrow aspirate showed 42% blasts at presentation and 77% and 55% after induction and reinduction, respectively, indicating persistent disease. Flow cytometry revealed an abnormal population of 75% at diagnosis, 67% post-induction, and 53% post-reinduction. Using a gating strategy for myeloblasts and monocytic population, the antigen expression at diagnosis showed CD34+, CD117+, CD13+, CD33+, CD38+, TdT+; HLA-DR partial+, myeloperoxidase (MPO) partial+, and CD13+, CD33+, CD38+, CD11c+, CD11b+, CD4+, CD64+, CD14+ immunophenotype, respectively. FISH results demonstrated marked RUNX1 amplification, del(7)(q31), trisomy 8, and CBFB signal loss. A myeloid tumor NGS panel identified a pathogenic TP53 gene variant (NM_000546.4:c.584T>C; p.Ile195Thr). The patient received standard chemotherapy (3 + 7 and AZA-VEN) but showed persistent refractory disease with continued cytopenias. Conclusion We report an exceptionally rare combination of genetic lesions in a young patient with refractory AML and marked RUNX1 amplification. Recognizing such cases may help improve and refine standard treatment modalities.