Association of RARA overexpression with monocytic features (MES) and venetoclax resistance markers in the SY-1425-201 clinical study ND unfit patients with AML. The MES and venetoclax resistance–associated features were profiled in ND unfit patients with AML. RARA-positive patients (red) were significantly enriched for features associated with venetoclax resistance including a high MES (left, y-axis), and low BCL2 (middle, y-axis) and high MCL1 expression (exp) (right, y-axis) compared with RARA-negative patients (blue). (A) Eighty percent (15/19) of RARA-positive patients and 17% (4/24) of RARA-negative patients are classified as monocytic by MES (MES > 0.5). (B) The majority of RARA-positive ND unfit patients with AML who achieved CR/CRi with tamibarotene plus azacitidine have a monocytic phenotype (high MES) associated with venetoclax resistance, which includes lower BCL2 and higher MCL1 expression.