"Root"ing for successful T-ALL treatment

In this issue of Blood, Anand et al provide compelling evidence that resistance to Notch inhibitor therapy in early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) occurs as a result of an activated phosphatidylinositol 3-kinase (PI3K) pathway. To further decipher the resistance mechanism, the investigators performed single-cell RNA sequencing analysis on the bone marrow of 5 patients treated with the γ-secretase inhibitor (GSI) BMS-906024 and found 13 different cell clusters, of which 6 were specific to leukemia patients.