Eriko Nagasawa

Vitamin K2 modulates differentiation and apoptosis of both myeloid and erythroid lineages

Vitamin K2 (VK2) can improve cytopenia in some patients with myelodysplastic syndrome (MDS). Although it is well known that VK2 induces differentiation and apoptosis in acute myeloid leukemia (AML) cell lines, little is known about its effect on normal hematopoietic progenitors. The effects of VK2 on primary myeloid and erythroid progenitors were examined. Mobilized CD34‐positive cells from peripheral blood were used for the examination of myeloid lineage cells, and erythroid progenitors purified from peripheral blood were used for erythroid lineage cells. VK2 upregulated the expressions of myeloid markers CD11b and CD14, and increased the mRNA expression levels of CCAAT/enhancer binding protein‐α (C/EBPα) and PU.1 in myeloid progenitors. In erythroid progenitors, VK2 did not show a significant effect on differentiation. However, VK2 exhibited an anti‐apoptotic effect on erythroid progenitors under erythropoietin depletion. This anti‐apoptotic effect was restricted to normal erythroid progenitors and was not shown in erythroleukemic cell line AS‐E2. Steroid and xenobiotic receptor (SXR), which was recently identified as a receptor of VK2, was expressed on myeloid progenitors, and the SXR agonist rifampicin (RIF) also upregulated CD11b and CD14 expressions on myeloid progenitors. These results indicate that SXR is involved in the effect of VK2 on myeloid progenitors. The major effect of VK2 on myeloid progenitors was promoting differentiation, whereas its anti‐apoptotic effect seemed to be dominant in erythroid progenitors. Although the detailed mechanism of VK2’s effect on differentiation or apoptosis of hematopoietic progenitors remains unknown, the effect of VK2 therapy in patients with MDS could be partly explained by these mechanisms.

Successful Treatment with Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Acute Myeloid Leukemia Complicated with Pulmonary Infection

We describe the case of a 48-year-old man with acute myeloid leukemia complicated with pulmonary infection that was successfully treated by nonmyeloablative allogeneic peripheral blood stem cell transplantation with conditioning by low-dose total body irradiation and fludarabine. The disease was diagnosed immunophenotypically as myeloid/natural killer cell precursor acute leukemia. After two courses of induction therapy, complete remission was achieved. However, the patient developed pneumonia from prolonged severe neutropenia. Nonmyeloablative allogeneic transplantation was performed because of the active pulmonary infection and the patients poor performance status. Myelosuppression after transplantation was mild, and the pulmonary infiltration was well controlled during the course of treatment. At the time of this report the patient was an outpatient in our clinic, and on day 500, his disease was in remission with well-controlled chronic graft-versus-host disease. Nonmyeloablative transplantation may provide a new therapeutic strategy for treating patients with active infection who cannot tolerate conventional transplantation with high-dose chemoradiotherapy.