BCR-ABL1 Positive B-ALL Can Undergo T-cell Lineage Shift to Become CD19 Negative T-ALL

Lineage shifts in acute lymphoblastic leukemia (ALL) are anti-CD19 directed therapy. They presented 2 cases of BCRuncommon and if they occur usually involve a switch from lymphoid to myeloid lineage. Here we report the observation of a Bto T-cell switch in a BCR-ABL1 positive B-ALL that was engrafted in immune deficient NOD.Cg-PrkdcIl2rg/SzJ (NSG) mice. We studied the engraftment of 4 BCR-ABL1 positive B-ALL cases (Table 1), and observed the unexpected appearance of a BCR-ABL1 positive T-ALL for 1 of the 4 cases (XC49). These data indicate that a switch from B-ALL to T-ALL is possible, and that this could be a novel mechanism to develop resistance against anti-CD19 directed therapy in some B-ALL cases. Indeed, with the introduction of CD19-directed immunotherapy for the treatment of B-cell malignancies, clinicians were suddenly confronted with previously unobserved tumor escape mechanisms. More and more patients present themselves at relapse with a downregulation or alteration of the CD19 surface antigen on their malignant cells or with an acquired extramedullary invasion. In a recent study, Nagel et al described an alternative escape route for malignant B-ALL cells after receiving