Аннотация:Summary The leukaemia‐specific fusion oncoprotein RUNX1/RUNX1T1 (AML1/ETO), resulting from the chromosomal translocation (8;21) in acute myeloid leukaemia (AML), imposes a striking genotype–phenotype relationship upon this distinct subtype of AML, which is mediated by multiple, co‐ordinate downstream effects induced by this chimeric transcription factor. We previously identified the LAT2 gene, encoding the adaptor molecule LAT2 (NTAL, LAB), which is phosphorylated by KIT and has a role in mast cell and B‐cell activation, as a target of the repressor activity of RUNX1/RUNX1T1. These results were confirmed and extended by demonstrating downregulation of the LAT2 protein in response to conditional RUNX1/RUNX1T1 expression, and its absence in primary AML with the t(8;21). In contrast, in a cohort of 43 AML patients, higher levels of LAT2 were associated with myelomonocytic features. Differentiation of HL‐60 and NB4 cells towards granulocytes by all trans ‐retinoic acid (ATRA) resulted in downregulation of LAT2; conversely, it was upregulated during phorbol ester‐induced monocytic differentiation of HL‐60 cells. Forced expression of LAT2 in Kasumi‐1 cells resulted in a striking block of ATRA‐ and phorbol ester‐induced differentiation, implicating disturbances of the graded expression of this adaptor molecule in the maturation block of myeloid leukaemia cells.
