The aim of this review is to summarize our experience and the current knowledge on the clinical results of Indirubin, a minor active constituent of a well-know traditional Chinese prescription, Ganggui Luhui Wan, and its analogue, Meisoindigo, in the treatment of chronic myelogenous leukemia (CML) in China. Indirubin and meisoindigo induced hematologic remission in patients with chronic phase (CP) CML as effective as hydroxyurea and busulfan, in addition, there were no significant differences in median duration of CP, median survival and blast crisis at 60 months from diagnosis in indirubin, meisoindigo, hydroxyurea and busulfan treated groups. However, when meisoindigo was combined with hydroxyurea, there was evidence of a significantly prolonged median duration of CP, median survival and a reduced incidence of blast crisis at 60 months compared with busulfan, meisoindigo and hydroxyurea alone. The critical mechanisms of indirubin and meisoindigo action have not yet been identified. Both antiproliferative and induced apoptosis mechanisms have been described. Further research, especially randomized trials, are required to confirm the role of indirubin and meisoindigo in the treatment of CML.

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Human dermal papilla (DP) cells have been studied extensively when grown in the conventional monolayer. However, because of great deviation from the real in vivo three-dimensional (3D) environment, these two-dimensional (2D) grown cells tend to lose the hair-inducible capability during passaging. Hence, these 2D caused concerns have motivated the development of novel 3D culture techniques to produce cellular microtissues with suitable mimics. The hanging-drop approach is based on surface tension-based technique and the interaction between surface tension and gravity field that makes a convergence of liquid drops. This study used this technique in a converged drop to form cellular spheroids of dermal papilla cells. It leads to a controllable 3Dspheroid model for scalable fabrication of inductive DP microtissues. The optimal conditions for culturing high-passaged (P8) DP spheroids were determined first. Then, the morphological, histological and functional studies were performed. In addition, expressions of hair-inductive markers including alkaline phosphatase, α-smooth muscle actin and neural cell adhesion molecule were also analyzed by quantitative RT-PCR, immunostaining and immunoblotting. Finally, P8-DP microtissues were coimplanted with newborn mouse epidermal cells (EPCs) into nude mice. Our results indicated that the formation of 3D microtissues not only endowed P8-DP microtissues many similarities to primary DP, but also confer these microtissues an enhanced ability to induce hair-follicle (HF) neogenesis in vivo. This model provides a potential to elucidate the native biology of human DP, and also shows the promising for the controllable and scalable production of inductive DP cells applied in future follicle regeneration.

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Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0566-8) contains supplementary material, which is available to authorized users.

Background Recent evidence suggests that resistance to CD19 chimeric antigen receptor (CAR)-modified T cell therapy may be due to the presence of CD19 isoforms that lose binding to the single-chain variable fragment (scFv) in current use. As such, further investigation of CARs recognize different epitopes of CD19 antigen may be necessary. Methods We generated a new CD19 CAR T (HI19α-4-1BB-ζ CAR T, or CNCT19) that includes an scFv that interacts with an epitope of the human CD19 antigen that can be distinguished from that recognized by the current FMC63 clone. A pilot study was undertaken to assess the safety and feasibility of CNCT19-based therapy in both pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL). Results Data from our study suggested that 90% of the 20 patients treated with infusions of CNCT19 cells reached complete remission or complete remission with incomplete count recovery (CR/CRi) within 28 days. The CR/CRi rate was 82% when we took into account the fully enrolled 22 patients in an intention-to-treat analysis. Of note, extramedullary leukemia disease of two relapsed patients disappeared completely after CNCT19 cell infusion. After a median follow-up of 10.09 months (range, 0.49–24.02 months), the median overall survival and relapse-free survival for the 20 patients treated with CNCT19 cells was 12.91 months (95% confidence interval [CI], 7.74–18.08 months) and 6.93 months (95% CI, 3.13–10.73 months), respectively. Differences with respect to immune profiles associated with a long-term response following CAR T cell therapy were also addressed. Our results revealed that a relatively low percentage of CD8+ naïve T cells was an independent factor associated with a shorter period of relapse-free survival (p = 0.012, 95% CI, 0.017–0.601). Conclusions The results presented in this study indicate that CNCT19 cells have potent anti-leukemic activities in patients with R/R B-ALL. Furthermore, our findings suggest that the percentage of CD8+ naïve T cells may be a useful biomarker to predict the long-term prognosis for patients undergoing CAR T cell therapy. Trial registration ClinicalTrials.gov: NCT02975687; registered 29 November, 2016. https://clinicaltrials.gov/ct2/keydates/NCT02975687

Aim: To explore the feasibility of human placenta extracellular matrix (HPECM) hydrogel in restoring the hair-inductive capacity of high-passaged (P8) dermal papilla cells (DPCs) for hair follicle regeneration. Materials & methods: HPECM hydrogel was prepared following decellularization and enzymatic solubilization treatment. DPCs isolated from human scalp were cultured in 2D and 3D environments. The hair-inductive ability of DPCs was assessed by quantitative RT-PCR, immunofluorescence staining, immunoblotting and patch assay. Results: DPCs (P8) formed spheres when cultured on the HPECM hydrogel. The expression levels of Versican, ALP, and β-catenin were restored in the DP spheres. HPECM hydrogel-cultured DP spheres co-grafted with newborn mouse epidermal cells regenerated new hair follicle. Conclusion: HPECM hydrogel successfully restores the hair-inductive capacity of high-passaged DPCs.

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