BCL-xL plays a critical role in the survival of JAK2-mut AML cell lines and patients with post-MPN AML. (A) BCL2L1 mRNA expression in AML cell lines in the Cancer Cell Line Encyclopedia database. (B) When the cell lines shown in panel A were grouped, JAK2-mut cell lines had significantly higher BCL2L1 expression than other AML cell lines. ∗P < .05. (C) BCL2L1 CRISPR gene knockout (KO) effect in AML cell lines in the Public Avana 21Q2 (DepMap) data set. More negative value corelate a stronger dependence. (D) When the cell lines shown in panel C were grouped, JAK2-mut cell lines had significantly lower BCL2L1 CRISPR gene scores than other AML cell lines. More negative values indicate stronger dependence. ∗P < .05. (E) Proliferation curves of JAK2-mut cell lines (SET2 and HEL) after BCL2L1 KO. (F) Proliferation curves of JAK2-WT AML cell lines (THP1 and OCI-AML3) after BCL2L1 gene KO. (G) RNA-seq analysis of BCL2L1 in patient data in the Beat AML 2.0 cohort. Cases were stratified according to AML with history of previous MPN (n = 28), prior MDS/MPN overlap (n = 24), prior MDS (n = 63), de novo AML (n = 323), or therapy-related AML (n = 53). Patients with prior MPN showed significantly higher BCL2L1 expression than patients with de novo AML. ∗∗P < .01. RLU, relative light unit; RPKM, reads per kilobase million; TPM, transcripts per million.