High Expression of RhoBTB3 Predicts Favorable Chemothrapy Outcomes in non-M3 Acute Myeloid Leukemia.

Background: The expression patterns and prognostic significance of the Rho family GTPases in acute myeloid leukemia have not been systematically studied yet. Methods: In our study, we analyzed the expression patterns of 21 Rho family GTPases gene members in AML patients based on GEPIA database. 10 gene members with significant differential expression in AML tissue and healthy tissue were selected for subsequent research. Survival curve analysis in TCGA and GEO dataset preliminary showed that RhoBTB3 is related with the prognosis of non-M3 AML patients. The differential expression of RhoBTB3 on AML bone marrow and normal bone marrow was verified by RT-qPCR. We performed Kaplan-Meier survival analysis and Multivariate Cox analysis to assess the prognostic value of RhoBTB3 in non-M3 AML patients with different treatment regimens. Gene functional enrichment analysis of RhoBTB3 was performed using GO, KEGG and PPI network. Results: The AML patients from TCGA database were partitioned into 2 groups based on different treatment regimens: chemotherapy group and allo-HSCT group. In chemotherapy group, patients with higher expression level of RhoBTB3 showed relatively longer OS and EFS, multivariate Cox analysis revealed high RhoBTB3 mRNA expression as an independent favorable prognostic factor. However, in allo-HSCT group, no significant difference of OS and EFS were found between RhoBTB3 high and low subgroups. Meanwhile, allo-HSCT could circumvent the unfavorable prognosis that was associated with downregulation of RhoBTB3. Functional enrichment analysis showed the association of RhoBTB3 expression with several fundamental physiological components and pathways, including extracellular matrix components, extracellular structure organization, and cytokine-cytokine receptor interaction. Conclusions: Our study identified RhoBTB3 as a prognostic marker and may aid in the selection of the appropriate treatment options between chemotherapy and allo-HCST in non-M3 AML patients. Further researches are necessary to clarify the involvement of RhoBTB3 in the pathogenesis of AML.

Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease.

Recent evidence indicates that p53 plays a protective role against various systemic autoimmune diseases by suppressing pro-inflammatory cytokine production and reducing the number of pathogenic T cells. However, whether abnormal p53 expression participates in the development of acute graft-versus-host disease (aGVHD) remains unclear. In this study, we demonstrated that p53 was downregulated in CD4+ T cells from patients with aGVHD compared with the non-aGVHD group. Furthermore, we confirmed that low expression of CCCTC-binding factor (CTCF) in CD4+ T cells from aGVHD cases is an important factor affecting histone H3K9/K14 hypoacetylation in the p53 promoter and p53 downregulation. Restoring CTCF expression in CD4+ T cells from aGVHD patients increased p53 amounts and corrected the imbalance of Th17 cells/Tregs. Taken together, these results provide novel insights into p53 downregulation in CD4+ T cells from aGVHD patients.

[Peripheral blood stem cell transplantation from HLA-mismatched unrelated donor or haploidentical donor for the treatment of X-linked agammaglobulinemia].

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8+ T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19+ B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.