Ventura Antonio Benedetto, Loconte Tiziana, Negri Antonio, Viggiano Luigi, Fiermonte Giuseppe, Ciavarella Sabino, Guarini Attilio, Volpe Giacomo
Hematology and Cell Therapy Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Department of Biology, University of Bari "Aldo Moro", Bari, Italy.
Cell Death Discov. 2025 Jun 12;11(1):276. doi: 10.1038/s41420-025-02551-4.
The MAFB protein, a member of the MAF family of bZip transcription factors, plays a pivotal role in various biological processes, including cell differentiation, development, and homeostasis. Characterized by its selective expression in monocytes and macrophages, MAFB has been shown to play a crucial role during myeloid lineage differentiation, acting as a critical determinant in the transition from multipotent progenitors to fully differentiated monocytes. By modulating the expression of genes associated with immune activation and inflammation, MAFB plays a vital role in maintaining immune homeostasis and responding to pathogenic challenges. Dysregulation of MAFB expression or function has been implicated in several pathological conditions, including hematological malignancies and metabolic disorders. In particular, aberrant MAFB activity has been associated with the progression of diseases such as multiple myeloma and acute myeloid leukemia as well as other solid tumors, where it may contribute to the survival and proliferation of malignant cells, thereby promoting disease progression. MAFB and downstream targets of its transcriptional network are now being regarded as predictive biomarkers for certain types of tumors as well as being considered as potential therapeutic targets for cancer treatment. In this review, we summarize current knowledge on both physiological and pathological roles of MAFB and highlight the impact of its deregulation on hematological cancer initiation and progression.
MAFB蛋白是bZip转录因子MAF家族的成员之一，在包括细胞分化、发育和体内平衡在内的各种生物学过程中发挥着关键作用。MAFB的特点是在单核细胞和巨噬细胞中选择性表达，已证明其在髓系谱系分化过程中起关键作用，是多能祖细胞向完全分化的单核细胞转变的关键决定因素。通过调节与免疫激活和炎症相关的基因表达，MAFB在维持免疫稳态和应对病原体挑战方面发挥着至关重要的作用。MAFB表达或功能失调与多种病理状况有关，包括血液系统恶性肿瘤和代谢紊乱。特别是，MAFB活性异常与多发性骨髓瘤和急性髓系白血病等疾病以及其他实体瘤的进展有关，在这些疾病中，它可能有助于恶性细胞的存活和增殖，从而促进疾病进展。MAFB及其转录网络的下游靶点现在被视为某些类型肿瘤的预测生物标志物，同时也被认为是癌症治疗的潜在治疗靶点。在本综述中，我们总结了关于MAFB生理和病理作用的当前知识，并强调了其失调对血液系统癌症起始和进展的影响。
