Mcl1, short for myeloid cell leukemia 1, is an anti-apoptotic protein belonging to the BCL2 family. It plays a crucial role in regulating cell survival, with its dysregulation involved in many physiological and pathological processes such as tumor drug resistance, tissue homeostasis, and programmed cell death [3]. It is commonly expressed in hematologic cancers and is also associated with pathways like mitochondrial oxidative phosphorylation, which impacts processes such as the maintenance of cancer stem cells [1,2].

In various cancers, Mcl1 has been shown to have significant effects. In triple-negative breast cancer (TNBC), it cooperates with MYC to promote chemotherapy-resistant cancer stem cells through regulation of mitochondrial oxidative phosphorylation [2]. High Mcl1 expression contributes to chemotherapy resistance and poor prognosis in TNBC, and a 4-member gene signature has been identified to predict Mcl1 inhibitor sensitivity [6]. In acute myeloid leukemia (AML), Mcl1 directly binds to Hexokinase 2 on the outer mitochondrial membrane, regulating cell metabolism, and high levels of certain metabolic features along with Mcl1 are linked to shorter overall survival [4]. In colorectal carcinoma, chemotherapy-induced Mcl1 nuclear translocation confers chemoresistance, while also exposing a Bcl-xL co-dependency [5].

In conclusion, Mcl1 is a key anti-apoptotic protein with its dysregulation being closely associated with cancer development and chemoresistance, especially in TNBC, AML, and colorectal carcinoma. Understanding Mcl1's functions through various in vivo studies helps in developing targeted therapeutic strategies for these diseases.