Issue Archive

The progression from monoclonal gammopathy to smoldering myeloma and then to multiple myeloma is associated with minimal genetic changes and relies primarily on changes in the marrow microenvironment. Nakamura and colleagues review the current understanding of the modulation of the immune environment that allows malignant plasma cells to evade immune elimination and promote disease progression.

Puerta-Alcalde and colleagues discuss their approach to the challenging problem of stem cell transplantation for patients with a history of invasive fungal disease.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an Epstein-Barr virus–positive lymphoma with poor prognosis that may respond to immunomodulatory therapy. Kim and colleagues report the results of a phase 2 study of the anti–programmed cell death ligand 1 (PD-L1) antibody avelumab in 21 patients with relapsed or refractory ENKTL. While nonresponders showed rapid progression, 25% of patients achieved complete remission, with response correlated with tumor PD-L1 expression.

The authors investigated the importance of cytokine stimulation in the evolution of hematopoietic stem cells with a leukemogenic mutation in c-MYC to AML. They demonstrated that in the absence of cytokine stimulation, transduction of human CD34⁺ cells with an MYC vector does not lead to AML in immunodeficient mice. However, transduction of both primitive stem cells and later progenitors with a mutant c-MYC rapidly induces AML in the presence of human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Weisel et al report an analysis of B-cell compartments across multiple tissues from healthy cadaveric donors and demonstrated that B cells in tissues are distinct from B cells circulating in peripheral blood. They defined several distinct populations of B cells residing in different tissues, including a distinct subtype of tissue-resident memory B cells restricted to the gut.

Oberbeck et al investigated the immunopathologic characteristics of T-cell prolymphocytic leukemia (T-PLL), a poor-prognosis lymphoproliferative neoplasm. They describe T-PLL as a proliferation of memory-type T cells with constitutive activation of the TCL1A oncogene that has hypersensitive response to T-cell receptor (TCR)–mediated activation and loss of negative-regulatory TCR coreceptors. This leads to accumulation of apoptosis-resistant hyperproliferative tumor cells.

Primary mediastinal large B-cell lymphoma is a rare lymphoma subtype associated with bulky mediastinal mass and usually presents in young females. Its prognosis has been greatly improved by adding rituximab to chemotherapy and radiotherapy (RT). Investigators from the British Columbia Cancer Centre report results of positron-emission tomography (PET)–directed RT following chemoimmunotherapy, identifying a subset of patients with excellent prognosis without radiation.

Myelodysplastic syndromes (MDSs) and secondary acute myeloid leukemia (AML) carrying TP53 mutations have a particularly dismal prognosis. The authors delineate the immunologic features of this subset of myeloid malignancy, demonstrating that TP53-mutant MDSs/AMLs display an immunosuppressive phenotype portending poor prognosis, characterized by upregulated PD-L1 expression and reduced marrow cytotoxic T cells. Although early studies of immunotherapy in MDS/AML have been disappointing, these studies suggest that immunomodulation may have an impact in this subset of myeloid malignancy.

Sharda et al explored the mechanism of von Willebrand factor (VWF) packaging into and release from Weibel-Palade bodies (WPBs) by defining the interaction of biogenesis of lysosome-related organelle-2 (BLOC-2) and the exocyst complex. BLOC-2 and exocyst bind to one another and facilitate formation of WPBs; they have divergent influences on WBP release, with BLOC-2 permissive for, and exocyst preventing, WPB release. This suggests that modulation of exocyst could increase VWF release.