Eriko Sada

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.

Composite gastrointestinal lymphoma consisting of diffuse large B-cell lymphoma and peripheral T-cell lymphoma

Composite lymphomas are defined as two different types of lymphomas presenting in the same anatomic site [1]. A rare case of a composite gastrointestinal lymphoma consisting of diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) is presented. A 65-year-old woman was diagnosed with mucosaassociated lymphoid tissue lymphoma of the duodenum in 2001. Eradication therapy for Helicobacter pylori resulted in complete remission of the lymphoma. After 4 years, she was admitted to our hospital due to hematemesis in December 2005. The levels of hemoglobin and soluble interleukin-2 receptor were 10.4 g/dL and 938.1 U/mL, respectively. Endoscopic examination revealed multiple ulcers in the stomach and ileum. On microscopy, both gastric and ileal ulcers showed diffuse proliferation of large lymphoid cells, which were positive for CD20, CD79a, and Epstein–Barr virus (EBV) encoded RNA-1 (EBER-1) in situ hybridization (ISH) and negative for CD3 and CD45RO (Fig. 1a–d). These findings were compatible with EBV-positive DLBCL of the elderly, according to the new WHO classification [2]. After 3 courses of combination chemotherapy (pirarubicin, vincristine, cyclophosphamide and prednisolone; THP-COP) with rituximab, the ileal ulcers disappeared, but the area of the gastric lymphoma enlarged. A partial gastrectomy was performed with a diagnosis of perforation of the stomach in April 2006. Unexpectedly, pathological examination of the resected specimen demonstrated diffuse proliferation of smallto large-sized lymphocytes with T-cell markers (positive for CD3, CD4, CD45RO, CD56 and TIA-1, and negative for CD8, CD20, CD79a and EBER-ISH, Fig. 1e–h). The diagnosis of PTCL was made, and the distribution of the disease and strong positivity of TIA-1 suggested enteropathyassociated T-cell lymphoma. Since the size of the lymphoma cells was mainly small to medium and they were positive for CD56, we speculated that the lymphoma could be classified into enteropathy-associated T-cell lymphoma type 2 [3, 4]. However, the mucosa of the specimen was almost destroyed and the distribution pattern was not clear. Retrospectively, we performed PCR analysis of T-cell receptor (TCR) gamma chain gene in the gastric specimen at the DLBCL stage in 2005 and PTCL stage in 2006 (Fig. 2). Although scattered T cells were present in the specimen, rearrangement of TCR was not detected. On the other hand, strong rearranged band was detected at the PTCL stage. Since PTCL was diagnosed during the course of chemotherapy against DLBCL and residual B-cell disease could not be denied after gastrectomy, the patient was given 2 courses of consolidation chemotherapy (etoposide, methylpredonisolone, cytarabine and cisplatin; ESHAP) with rituximab. Achievement of complete remission was confirmed by 18[F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in June 2006. However, Y. Tachikawa M. Shiratsuchi E. Sada K. Idutsu J. Kiyasu R. Takayanagi Y. Abe (&) Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: abey@intmed3.med.kyushu-u.ac.jp