The emerging role of cancer-associated fibroblasts in hematological malignancies: from their influence on tumor progression and drug resistance to novel therapeutic opportunities.

The tumor microenvironment (TME) plays a critical role at all stages of tumor progression. Cancer-associated fibroblasts (CAFs), as the main components of this environment, display diversities in origin, phenotype, and function, which contribute to cancer progression by regulating the tumor cell biology via cell-cell contact, releasing numerous regulatory elements such as growth factors (GFs), cytokines, and chemokines, and even remodeling the extracellular matrix (ECM). In this Review, we discuss the current understanding of CAFs' pro- or anti-tumor functions in various hematological malignancies, including acute and chronic leukemia, lymphoma, and multiple myeloma (MM). The accumulating evidence highlighted that CAFs not only are implicated in these neoplasms' initiation, development, and metastasis but also are involved in chemoresistance to various chemotherapy drugs such as daunorubicin and bortezomib. Intriguingly, cell culture-based methods' results outlined that targeting signaling pathways that are used by CAFs to exert their pro-tumorigenic effects could be exploited in favor of tumor inhibition, which requires more investigation. Therefore, this therapeutic approach should be considered in future studies to develop a novel targeted therapy in hematological malignancies.