Bortezomib resistance and MUC1 in myeloma.

immunohistochemistry for GATA3 on an independent series of cases, Wang et al also showed that GATA3 expression, evidenced in almost half of the cases, identifies a high-risk subset of PTCL, NOS. Although the findings in these 2 independent cohorts are convergent, it will be useful to confirm the clinical correlation of the GATA3 vs TBX21 profiles in another series of PTCL, NOS patients, if possible in the setting of a trial where homogeneous therapy is applied. Having shown that molecular signatures in PTCL, NOS have a clinical impact, an important question is whether there is a rationale to suggest that these molecular subgroups may benefit from distinct, innovative, and potentially more efficient therapies. Investigating whether the molecular subgroups differ in terms of pathogenesis and oncogenic pathways is a prerequisite to identify novel druggable targets. Evidence for enrichment in intracellular pathways such as the phosphoinositide 3-kinase-associated gene signature in the GATA3 subgroup provides a basis for intervention with specific inhibitors. The experimental data provided in the study by Wang et al point at the role of the tumor microenvironment and how Th2 cytokines may contribute to shaping the phenotype of both the lymphoma cells and tumor-associated macrophages, functionally polarized to promote neoplastic growth, suggesting that tumor microenvironment may represent a therapeutic target. Finally, novel recurrent mutations expected to be discovered by the ongoing high-throughput and deep sequencing studies may segregate with molecular subgroups and possibly provide insights into novel therapies. Conflict-of-interest disclosure:The authors declare no competing financial interests. n