Solute carrier family 12 member 7 splice variant (sv-SLC12A7) (sv-SLC12A7)

sv-SLC12A7 is a leukemia-specific splice variant of the Solute carrier family 12 member 7 (SLC12A7), also known as KCC4 [2, 4]. While the canonical SLC12A7 protein functions as a potassium-chloride cotransporter involved in ion homeostasis and cell volume regulation, this specific splice variant is characterized by a unique protein domain that is highly expressed on the surface of blast cells and leukemic stem cells in Acute Myeloid Leukemia (AML) [2, 7]. Its expression is particularly elevated in AML patients harboring epigenetic mutations, such as those in the SRSF2 gene [4, 9]. Due to its minimal presence in normal hematopoietic and non-hematopoietic tissues, sv-SLC12A7 is an attractive therapeutic target for immunotherapies, including chimeric antigen receptor (CAR) T-cell therapy and monoclonal antibodies [2, 10]. Targeting this variant aims to selectively eradicate leukemic cells while sparing healthy tissues, addressing a critical need for more precise treatments in AML [7, 11]. Research has demonstrated that sv-SLC12A7-directed CAR-T cells can effectively eradicate leukemic cells in xenograft models, suggesting significant potential for clinical development [2, 4].

Other names

KCC4 splice variantPotassium-chloride cotransporter 4 splice variantSLC12A7 isoformsv-KCC4

Targeted immunotherapy via chimeric antigen receptor (CAR) T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC)