Axin is known to have an important role in the degradation of b-catenin in the Wnt pathway. Here, we reveal a new function of Axin at the centrosome. Axin was localized to the centrosome in various cell lines and formed a complex with c-tubulin. Knockdown of Axin reduced the localization of c-tubulin and c-tubulin complex protein 2-components of the c-tubulin ring complex-to the centrosome and the centrosomal microtubule nucleation activity after treatment with nocodazole. These phenotypes could not be rescued by the reduction in the levels of b-catenin. Although the expression of Axin rescued these phenotypes in Axin-knockdown cells, overexpression of Axin2, which is highly homologous to Axin, could not. Axin2 was also localized to the centrosome, but it did not form a complex with c-tubulin. These results suggest that Axin, but not Axin2, is involved in microtubule nucleation by forming a complex with c-tubulin at the centrosome.

The DDX41 gene, encoding a DEAD-box type ATP-dependent RNA helicase, is rarely but reproducibly mutated in myeloid diseases. The acquired mutation in DDX41 is highly concentrated at c.G1574A (p.R525H) in the conserved motif VI located at the C-terminus of the helicase core domain where ATP interacts and is hydrolyzed. Therefore, it is likely that the p.R525H mutation perturbs ATPase activity in a dominant-negative manner. In this study, we screened for the DDX41 mutation of CD34-positive tumor cells based on mRNA sequencing and identified the p.R525H mutation in three cases among 23 patients. Intriguingly, these patients commonly exhibited acute myeloid leukemia (AML) with peripheral blood cytopenias and low blast counts, suggesting that the mutation inhibits the growth and differentiation of hematopoietic cells. Data from cord blood cells and leukemia cell lines suggest a role for DDX41 in preribosomal RNA processing, in which the expression of the p.R525H mutant causes a certain ribosomopathy phenotype in hematopoietic cells by suppressing MDM2-mediated RB degradation, thus triggering the inhibition of E2F activity. This study uncovered a pathogenic role of p.R525H DDX41 in the slow growth rate of tumor cells. Age-dependent epigenetic alterations or other somatic changes might collaborate with the mutation to cause AML.

There is a controversy which short term high dose dexamethasone therapy (HDD) or standard dose prednisolone therapy as the initial treatment leads to long term efficacy in idiopathic thrombocytopenic purpura (ITP) patients. We conducted a multicenter, prospective trial to determine the efficacy and safety of short-term HDD in ITP patients aged 18-80 years with platelet counts of <20 × 10 9 /L, or <50 × 10 9 /L and bleeding symptoms.The primary endpoints are the proportion of complete response (CR) plus partial response (R) on day 180 after the completion of the 46-day HDD.Twenty-three patients were enrolled. Test for Helicobacter pylori (H.pylori) was positive for 6 patients, and negative for 17 patients. In positive patients, 5 were received successful H.pylori eradication therapy. The proportion of CR+R was 60.9% (14/23) with 90% confidence interval of 41.7-77.8%. For patients with positive H.pylori and successful eradication, proportion of CR+R was 80.0% (4/5). There was one grade 4 adverse event. Although we have enrolled relatively old, severe ITP patients with a median age of 63 years in this study, the efficacy was comparable to the reported clinical trials with HDD therapy.

A 20-year-old man with a 5-year history of acute lymphoblastic leukemia (ALL) was admitted to our hospital for severe pains in his bilateral groin and right shoulder. He had experienced these pains for 16 months. He underwent allogeneic stem cell transplantation in his second complete remission 13 months prior to hospitalization. He had received corticosteroid therapy both for ALL and for graft versus host disease for a long period (more than 13 months in total), and the total dose of corticosteroids exceeded 20 g in prednisolone equivalent at the time of the hospitalization. X-ray films of the hip joints revealed collapse of bilateral femoral heads. In addition, a subarticular radiolucent line (''crescent sign'') was also observed in an X-ray film of the right shoulder joint (Fig. 1). He was diagnosed with osteonecrosis of the femoral and humeral heads. A magnetic resonance image (MRI) showed a geographical high-intensity area spread to diaphysis, suggesting necrotic changes affecting an extensive area (Fig. 2). He was treated with narcotics for pain. Corticosteroids were reduced as rapidly as possible and maintained at a low dose to treat his adrenal insufficiency. However, his range of motion gradually decreased. Longterm corticosteroid use has been reported to be a risk factor for osteonecrosis of the humeral head, as well as the hip joint. The pathogenesis of steroid-induced osteonecrosis remains unclear, but ischemia from lipocyte hypertrophy or fat embolism has been postulated. The interval between corticosteroid administration and onset of symptom has been reported as between 6 and 18 months. Although the humeral head is the second most commonly affected site in osteonecrosis, it is often unrecognized, and its initial symptoms are often nonspecific. Removal of risk factors can reduce the risk of osteonecrosis to other joints. Thus,