Cell cycle dysregulation leads to uncontrolled cell proliferation and tumorigenesis. Understanding the molecular mechanisms underlying cell cycle progression can provide clues leading to the identification of key proteins involved in cancer development. In this study, we performed proteomics analysis to identify novel regulators of the cell cycle. We found that potassium channel tetramerization domain containing 12 (KCTD12) was significantly upregulated in M phase compared with S phase. We also found that KCTD12 overexpression not only facilitated the G2/M transition and induced cancer cell proliferation, but also promoted the growth of subcutaneous tumors and Ki-67 proliferation index in mice. Regarding the mechanism underlying these phenomena, cyclin-dependent kinase 1 (CDK1) was identified as an interacting partner of KCTD12 by immunoprecipitation and mass spectrometry analysis, which showed that KCTD12 activated CDK1 and Aurora kinase A (Aurora A) and that the effects of KCTD12 on CDK1 phosphorylation and cell proliferation were abrogated by cell division cycle 25B (CDC25B) silencing. In addition, Aurora A phosphorylated KCTD12 at serine 243, thereby initiating a positive feedback loop necessary for KCTD12 to exert its cancer-promoting effects. Furthermore, we analyzed the expression levels of various genes and the correlations between the expression of these genes and survival using tumor tissue microarray and Gene Expression Omnibus (GEO) data sets. The data showed that KCTD12 expression was significantly upregulated in cervical and lung cancers. More importantly, high KCTD12 expression was associated with larger tumor sizes, higher pathological stages and poor patient survival. Collectively, our study demonstrate that KCTD12 binds to CDC25B and activates CDK1 and Aurora A to facilitate the G2/M transition and promote tumorigenesis and that Aurora A phosphorylates KCTD12 at serine 243 to trigger a positive feedback loop, thereby potentiating the effects of KCTD12. Thus, the KCTD12-CDC25B-CDK1-Aurora A axis has important implications for cancer diagnoses and prognoses.

Few studies have presented a comparison of myeloablative cord blood transplantation (CBT) and HLA-identical sibling hematopoietic cell transplantation (HCT) for AML in a disease-specific analysis, and the evaluation of GvHD-free and relapse-free survival (GRFS) in AML patients after unrelated CBT has not been reported. A total of 162 consecutive AML patients receiving intensified myeloablative unrelated CBT (n = 107) or allogeneic PBSC transplantation (allo-PBSCT) or bone marrow transplantation (BMT) from an HLA-identical sibling donor (n = 55) were investigated. Neutrophil or platelet engraftment was slower in the CBT cohort compared with that in the allo-PBSCT/BMT cohort. The incidence of grade II-IV or grade III-IV acute GvHD (aGvHD) and transplant-related mortality (TRM) were not significantly different in the two cohorts. Compared with the allo-PBSCT/BMT cohort, the CBT cohort had a significantly lower rate of chronic GvHD (cGvHD) (13.7% vs 28.3%; P = 0.047) or extensive cGvHD (9.9% vs 24.1%; hazard ratio (HR) = 2.06, P = 0.039). The incidence of relapse at 5 years in the CBT cohort was significantly lower than that in the allo-PBSCT/BMT cohort (15.3% vs 36.1%; HR = 4.62, P = 0.009). The probabilities of overall survival and leukemia-free survival were similar between the two cohorts. The adjusted 5-year probability of GRFS was higher after CBT than that after allo-PBSCT/BMT (55.4% vs 39.2%; HR = 1.63, P = 0.042). The present study suggests that, for AML patients, intensified myeloablative unrelated CBT is associated with less cGvHD and a lower risk of relapse. In addition, these patients do not experience excessive TRM or severe aGvHD that translates into better GRFS compared with those patients who undergo HLA-identical sibling allo-PBSCT/BMT; this observation may reflect the clinical separation between cGvHD and GvL within our CBT protocol. INTRODUCTIONAllogeneic hematopoietic cell transplantation (allo-HCT) is a promising curative approach for treating high-risk or relapsed/ refractory AML. Unrelated cord blood transplantation (CBT) is increasingly being employed as an alternative transplant strategy for AML patients who lack a related or unrelated donor with an identical HLA type. Cord blood (CB) has some potential advantages, including the absence of donor risk, rapid accessibility and less rigorous requirement for HLA compatibility. Recently, reduced-intensity conditioning followed by CBT has been conducted for high-risk AML patients to decrease the early transplant-related mortality (TRM), 1,2 but the incidence of relapse was high (nearly 50%), and the long-term survival was very poor. New strategies should be further investigated to improve the antileukemic effect after CBT. We have reported that myeloablative CBT can result in improved survival and decreased relapse rates in adult or pediatric recipients with hematologic malignancies 3,4 compared with transplants from HLA-matched sibling donors (MSD); however, few studies have presented a comparative analysis of myeloablative CBT and allo-HCT fro...

This study included data from 185 consecutively treated patients, 16 years of age or older, who underwent myeloablative transplantation using unrelated umbilical cord blood (UCB) (UCB transplantation (UCBT), n = 70) or HLA-identical sibling donor peripheral blood stem cells alone or combined with bone marrow (BMT/PBSCT, n = 115) from October 2001 to December 2012. All patients received myeloablative regimens, cyclosporin A plus mycophenolate mofetil as prophylaxis for GVHD, and similar supportive care. Although hematopoietic recovery was significantly delayed after UCBT, the rate of neutrophil engraftment was comparable. The median follow-up was 53 months (range, 15-136 months) for BMT/peripheral blood SCT (PBSCT) recipients and 35 months (range, 10-123 months) for UCBT recipients. There were no significant differences in the cumulative incidence of grades III to IV acute GVHD, relapse rate, or 3-year probabilities of disease-free survival between patients receiving UCBT and those receiving BMT/PBSCT. However, the cumulative incidence of chronic and extensive chronic GVHD was lower in UCBT recipients. The rates of long-term survivors returning to school or work and off immunosuppressive therapy were significantly higher after UCBT, which indicated that long-term survivors who underwent UCBT had a higher quality of life.