For this reason, we report an exceptional case of a patient with a history of CML who progressed to myeloid BP driven by the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1 within 6 months from the initial diagnosis, which highlights the importance of understanding the biology and pathogenesis of hematological diseases to offer the best available treatment. The gene discussed is RUNX1T1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.