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The article discusses research that defined the expression of PD-L1 and PD-1 in clonal PCs and T and natural killer (NK) cells on bone marrow (BM) aspirates from monoclonal gammopathy of undetermined significance (MGUs) and multiple myeloma (MM) patients at diagnosis following treatment and upon relapse using standardized multidimensional flow cytometry (MFC). It suggests that PD-L1 can operate as an immune checkpoint in the tumor microenvironment.

The development of resistance to therapy is unavoidable in the history of multiple myeloma patients. Therefore, the study of its characteristics and mechanisms is critical in the search for novel therapeutic approaches to overcome it. This effort is hampered by the absence of appropriate preclinical models, especially those mimicking acquired resistance. Here we present an in vivo model of acquired resistance based on the continuous treatment of mice bearing subcutaneous MM1S plasmacytomas. Xenografts acquired resistance to two generations of immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide) in combination with dexamethasone, that was reversible after a wash-out period. Furthermore, lenalidomide-dexamethasone (LD) or pomalidomide-dexamethasone (PD) did not display cross-resistance, which could be due to the differential requirements of the key target Cereblon and its substrates Aiolos and Ikaros observed in cells resistant to each combination. Differential gene expression profiles of LD and PD could also explain the absence of cross-resistance. Onset of resistance to both combinations was accompanied by upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway and addition of selumetinib, a small-molecule MEK inhibitor, could resensitize resistant cells. Our results provide insights into the mechanisms of acquired resistance to LD and PD combinations and offer possible therapeutic approaches to addressing IMiD resistance in the clinic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the examination of the presence of myelodysplastic syndrome (MDS)-associated phenotypic alterrations (MDS-PAs) in bone marrow (BM) samples from newly diagnosed patients referred immunophenotypic investigation of plasma cell (PC) neoplasia.

The article presents a study that characterizes and compares the highly tumor-specific rearranged immunoglobulin heavy chain genes (CDR3) region in patients with multiple myeloma (MM). Overview of the background of the study that observes 52 patients with MM and the progression as well as monoclonality of the evolution of the condition is provided. The findings of the study which indicates that the CDR3 region remained constant across all states of disease evolution are offered.