Clinical features, pathophysiology, and management of acute myelopathy following CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed or refractory hematologic malignancies, but it comes with unique toxicities, notably cytokine release syndrome and ICANS (immune effector cell-associated neurotoxicity syndrome). As experience with CAR T-cell therapy grows, distinct and infrequent neurologic complications are becoming increasingly evident. Recently, reports of acute myelopathy after the administration of CAR T-cell therapies have been accumulating.

Outcomes of adults with refractory or relapsed acute myeloid leukemia treated with azacitidine and venetoclax compared to other therapies: a multicenter retrospective study.

This study reports characteristics and outcomes of adults who received Azacitidine-Venetoclax (AZA-VEN) compared to other salvage therapies (NO-AZA-VEN) as first salvage therapy for acute myeloid leukemia (AML). The clinical data of 81 patients with a diagnosis of relapsed or refractory AML were analyzed. The ORR was comparable for both groups (55% vs 57%,  = 0.

Extracellular Signal-Regulated Kinases: One Pathway, Multiple Fates.

This comprehensive review delves into the multifaceted aspects of ERK signaling and the intricate mechanisms underlying distinct cellular fates. ERK1 and ERK2 (ERK) govern proliferation, transformation, epithelial-mesenchymal transition, differentiation, senescence, or cell death, contingent upon activation strength, duration, and context. The biochemical mechanisms underlying these outcomes are inadequately understood, shaped by signaling feedback and the spatial localization of ERK activation.

Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response.