Low LEF1 expression is a biomarker of early T-cell precursor, an aggressive subtype of T-cell lymphoblastic leukemia.

: Early T-cell precursor (ETP) is the only subtype of acute T-cell lymphoblastic leukemia (T-ALL) listed in the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Patients with ETP tend to have worse disease outcomes. ETP is defined by a series of immune markers. The diagnosis of ETP status can be vague due to the limitation of the current measurement. In this study, we performed unsupervised clustering and supervised prediction to investigate whether a molecular biomarker can be used to identify the ETP status in order to stratify risk groups. We found that the ETP status can be predicted by the expression level of Lymphoid enhancer binding factor 1 (LEF1) with high accuracy (AUC of ROC = 0.957 and 0.933 in two T-ALL cohorts). The patients with ETP subtype have a lower level of LEF1 comparing to the those without ETP. We suggest that incorporating the biomarker LEF1 with traditional immune-phenotyping will improve the diagnosis of ETP.