Pathophysiology of ANKRD26-related thrombocytopenia and B-ALL recurrence after blinatumomab

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Shengwen Calvin Li and Hrishi Krishna Srinagesh on their latest articles published in Blood. Dr. Li discusses "Single-cell profiling of ANKRD26 thrombocytopenia reveals progenitor expansion and polyploid apoptosis via JUNB-p21". The study identifies reproducible abnormalities in progenitor expansion and increased apoptosis of polyploid megakaryocytes, and they propose a novel mechanism in which centrosomal over-expression of ANKRD26 drives polyploid megakaryocyte apoptosis through JUNB-mediated induction of p21 transcription. Dr. Srinagesh discusses "Blinatumomab nonresponse correlates with poor survival after brexucabtagene autoleucel in B-cell ALL" in which data collected by the Real-World Outcomes Collaborative of CAR-T in Adult ALL consortium showed that prior nonresponse to blinatumomab was associated with inferior survival after brexucabtagene in comparison to blinatumomab-naïve patients. Early CAR-T responses were uniformly high regardless of prior exposure or response. This highlights that resistance to blinatumomab may identify patients at higher risk of post–CAR T relapse despite excellent initial responses.