Study summary · research use only
FoxO1 signaling in B cell malignancies and its therapeutic targeting
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review (species not specified) discusses FoxO1 signaling in B cell malignancies and approaches to its therapeutic targeting. FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are described as traditionally considered tumor suppressors that also show oncogenic properties, with FoxO1 involved in B cell development, immunoglobulin gene rearrangement, B cell receptor structure, DNA damage control, cell cycle regulation, and germinal center reaction. The review describes FoxO1 regulation at transcriptional and post-transcriptional levels, and recurrent activating mutations (S22/T24) and aberrant nuclear export reported in B cell malignancies including ALL, AML, CLL, FL, DLBCL, MCL, BL, HL, and multiple myeloma, plus preclinical evidence for inhibitors including AS1708727, AS1842856, and cpd10.
Abstract
FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are a highly evolutionary conserved subfamily of the 'forkhead' box proteins. They have traditionally been considered tumor suppressors, but FoxO1 also exhibits oncogenic properties. The complex nature of FoxO1 is illustrated by its various roles in B cell development and differentiation, immunoglobulin gene rearrangement and cell-surface B cell receptor (BCR) structure, DNA damage control, cell cycle regulation, and germinal center reaction. FoxO1 is tightly regulated at a transcriptional (STAT3, HEB, EBF, FoxOs) and post-transcriptional level (Akt, AMPK, CDK2, GSK3, IKKs, JNK, MAPK/Erk, SGK1, miRNA). In B cell malignancies, recurrent FoxO1 activating mutations (S22/T24) and aberrant nuclear export and activity have been described, underscoring the potential of its therapeutic inhibition. Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10).
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