HOPX as a tumour‐suppressive protein in T‐cell acute lymphoblastic leukaemia.

Summary The homeodomain protein homeobox (<italic>HOPX</italic>), a multifaceted regulator of cellular functions and developmental processes, is predominantly expressed in stem cells across diverse tissues; it has also emerged as a tumour suppressor in various solid cancers. However, its role in haematological malignancies still remains undefined. This study aimed to elucidate its significance in T‐cell acute lymphoblastic leukaemia (T‐ALL). We firstly uncovered a novel link between reduced HOPX expression, its promoter hypermethylation and increased tumour burden in patients with T‐ALL, suggesting its tumour‐suppressive role. Next, we induced T‐ALL by transducing intracellular NOTCH1 (ICN1) into mice with either conditional knock‐in at the Rosa26 locus or knockout of Hopx. We found that T‐ALL development was markedly accelerated and impeded in backgrounds with low and high Hopx expression respectively. Further analysis revealed Hopx's roles in modulating the Wnt‐β‐catenin pathway, a pivotal regulator of the downstream Myc signalling involved in T‐ALL transformation and progression. [ABSTRACT FROM AUTHOR]