Rowan Higgs

Hematology: NPI-0052 and lenalidomide trigger apoptosis in multiple myeloma cells

recent evidence indicates that the novel 20s proteasome inhibitor nPi‐0052 (marizomib) triggers apoptosis in multiple myeloma (mm) cells, when given in combination with the immunomodulatory agent lenalidomide. this is significant because nPi‐0052 might offer a novel therapeutic option for patients resistant to bortezomib and lenalidomide. as a bicyclic β‐lactone γ‐lactam, nPi‐0052 is structurally and functionally different to bortezomib. “importantly, some patients cannot tolerate bortezomib or are resistant to this agent and therefore this new combination of nPi‐0052 and lenalidomide may be of clinical utility,” explains Dharminder Chauhan, lead investigator of the study. the researchers tested the effects of nPi‐0052 (2 nm) and lenalidomide (3 μm) on human mm cell lines and primary tumor cells from seven patients with mm who had relapsed following a variety of treatment regimens. they observed a significant decrease in cell viability only when both agents were used in combination. this result was due to an increase in apoptosis, as indicated by a marked increase in the annexin v+/propidium iodide– apoptotic cell population. Crucially, no increase in apoptosis was observed in normal peripheral blood mononuclear cells from the mm patients following exposure to the combined treatment. Chauhan’s team next investigated the mechanism by which nPi‐0052 triggers apoptosis in mm cell lines, and through the use of caspase inhibitors hematology nPi-0052 and lenalidomide trigger apoptosis in multiple myeloma cells

Hematology: Cancer-initiating cells identified in acute promyelocytic leukemia

Recent evidence has identified the murine equivalent of the elusive cancer-initiating stem cells thought to be responsible for relapse in patients with acute promyelocytic leukemia (APL). These cells, described in Blood by Florence Guibal and colleagues, can initiate and propagate disease by persisting in hematopoietic organs of mice with APL. “The cancer stem cell hypothesis proposes that relapses in [APL] and other cancers might be the result of inefficient therapeutic targeting of a small fraction of cells responsible for initiating and/or maintaining the bulk population of cancer cells,” say the authors.

Medical oncology: Carcinoembryonic antigen mRNA expression—a marker for early pancreatic cancer recurrence?

Medical oncology: Carcinoembryonic antigen mRNA expression—a marker for early pancreatic cancer recurrence?

Hematology: Synergistic effects of bortezomib and melphalan therapy in patients with multiple myeloma

Hematology: Synergistic effects of bortezomib and melphalan therapy in patients with multiple myeloma