Multiple myeloma (MM) is the second most prevalent hematologic malignancy. In the past few years, the survival of MM patients has increased due to the emergence of novel drugs and combination therapies. Nevertheless, one of the significant obstacles in treating most MM patients is drug resistance, especially for individuals who have experienced relapses or developed resistance to such cutting-edge treatments. One of the critical processes in developing drug resistance in MM is autophagic activity, an intracellular self-digestive process. Several possible strategies of autophagy involvement in the induction of MM-drug resistance have been demonstrated thus far. In multiple myeloma, it has been shown that High mobility group box protein 1 (HMGB1)-dependent autophagy can contribute to drug resistance. Moreover, activation of autophagy via proteasome suppression induces drug resistance. Additionally, the effectiveness of clarithromycin as a supplemental drug in treating MM has been reported recently, in which autophagy blockage is proposed as one of the potential action mechanisms of CAM. Thus, a promising therapeutic approach that targets autophagy to trigger the death of MM cells and improve drug susceptibility could be considered. In this review, autophagy has been addressed as a survival strategy crucial for drug resistance in MM.
Conventional immunohistochemistry (IHC) has long been regarded as the "gold standard" for the diagnosis of tissue pathology. However, the diagnostic-prognostic value of this technique is limited by factors such as high inter-observer variability, restricted labeling potential and insufficient availability of samples for testing (Tan et al., 2020). However, the emergence of multiplex immunohistochemistry/immunofluorescence (mIHC/IF) techniques has provided an opportunity to overcome many of these challenges. These techniques facilitate investigation of multiple biomarkers on a single slide as well as exploration of tissue-level biology, classification of cell-cell interactions, and identification of rare cellular phenotypes. mIHC/IF is also a powerful supplement to technologies such as next generation sequencing. As such, mIHC/IF holds the potential to revolutionize cancer therapies and diagnostic pathology (Tan et al., 2020; Hernandez et al.; Lazcano et al.; Parra). In this special edition of Frontiers in Molecular Biosciences we review the importance and clinical translational potential of mIHC/IF.The COVID-19 pandemic has resulted in an urgent need to understand the implications of myocardial involvement in disease mortality, necessitating detection of viral components within tissue samples. Chong et al., used a combination of mIHC/IF and molecular techniques to examine cardiac autopsy specimens from 12 intensive care unit (ICU) naïve, SARS-CoV-2 PCR-positive patients. These novel findings revealed histopathologic changes in coronary vessels, as well as inflammation of the myocardium in these patients. This study provided crucial insights into the characteristics of COVID-19 patients at risk of sudden death, and suggested the possibility of longterm complications in patients with persistent virus (Chong et al.).As well as detecting viral particles within tissue samples, mIHC/IF can be used to explore the tumour immune microenvironment (TIME). Through the development of a multiplex panel for the identification of proliferating B cells, follicular helper T cells, and follicular regulatory T cells, Boisson et al., demonstrated the power of mIHC/IF for studying marker co-localization in
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