Takaaki Maekawa

Donor cell leukemia arising from preleukemic clones with a novel germline DDX41 mutation after allogenic hematopoietic stem cell transplantation.

Donor cell leukemia arising from preleukemic clones with a novel germline DDX41 mutation after allogenic hematopoietic stem cell transplantation

Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis

Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as elevation in circulating cytokine levels, cellular interactions and genetic mutations. However, the underlying mechanism of MF still remains unknown. Recent studies have revealed that fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells, and the thrombopoietin (TPO)/myeloproliferative leukemia protein (MPL; TPO receptor) signaling pathway play a certain role in the development of MF. In the present study, we aimed to investigate the relationship between fibrocytes and MPL activation. We showed that TPO or a TPO receptor agonist directly induces fibrocyte differentiation using murine fibrocyte cell lines and a murine MF model. Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL activation contributes to the progression of MF. Furthermore, we revealed that SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were possible fibrocyte precursors and that these cells increased in number in MF patients not treated with ruxolitinib. Our findings confirmed a link between fibrocytes and the TPO/MPL signaling pathway, which could result in a greater understanding of the pathogenesis of MF and lead to the development of novel therapeutic interventions.

Delayed Onset Tumor Lysis Syndrome after Initial Pomalidomide Treatment in a Patient with Refractory Multiple Myeloma

An 82-year-old male with multiple myeloma developed tumor lysis syndrome (TLS) 9 days after initial pomalidomide and dexamethasone treatment (PomD). His prior therapy included melphalan and prednisolone; bortezomib and dexamethasone; and lenalidomide and dexamethasone without any TLS symptoms. PomD was administered due to myeloma progression, and his renal function improved gradually without acute adverse effects. However, on day 9, his renal function suddenly worsened, and serum lactate dehydrogenase, uric acid, potassium, and phosphorous levels were elevated. There were no symptoms of infection, or remarkable changes in urinary findings. After PomD was discontinued and hydration was started on the same day, his renal function improved immediately, and treatment was resumed on day 24. TLS is a relatively rare, but life-threatening, complication in multiple myeloma patients and this onset period is sometimes quite different from other hematological malignancies. In addition to myelosuppression, TLS is a critical adverse event of PomD that may have delayed onset.