LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

Macrophage regulation of graft-vs-host disease

Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell transplantation.Understanding of the immune cells’reaction in pathophysiology of GVHD has improved,but a review on the role of macrophages in GVHD is still absent.Studies have observed that macrophage infiltration is associated with GVHD occurrence and development.In this review,we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD,focusing on the macrophage recruitment and infiltration,macrophage polarization,macrophage secretion,and especially interaction of macrophages with other immune cells.We could conclude that macrophage recruitment and infiltration contribute to both acute and chronic GVHD.Based on distinguishing pathology of acute and chronic GVHD,macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic GVHD.However,the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage polarization.In addition,interaction of macrophages with alloreactive T cells plays an important role in acute GVHD.Meanwhile,the interaction among macrophages,B cells,fibroblasts,and CD4+T cells participates in chronic GVHD development.

Age-related modifications of macrophages influenced by “inflammageing”in graft vs. host disease

Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.

Efficacy and safety of tandem autologous stem cell transplantation in multiple myeloma:a retrospective single-center analysis

To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three decades.Tandem stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 months.More than two decades after its introduction,trials exploring the utility of tandem transplants have yielded mixed results.The role of tandem ASCT in multiple myeloma(MM)remains unclear and controversial.In the EMN02/HOVON95 study.

TCP1 regulates Wnt7b/β-catenin pathway through P53 to influence the proliferation and migration of hepatocellular carcinoma cells

Dear Editor,Molecular chaperones are critical mediators of oncogenesis and necessary for cell survival.1 The cytoplasmic chaperone TRiC(Tcomplex protein-1 ring complex,also known as CCT)comprises two back-to-back stacked rings,with each ring containing eight subunits(CCT1–CCT8).2 And the effects of CCT subunits on tumors may be different.However,the roles of the CCT1 subunit(also known as TCP1)in hepatocellular carcinoma(HCC)and its molecular mechanism have not been investigated thoroughly.Understanding these details can provide new ideas and strategies for treating HCC.

2021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy

Immune thrombocytopenia(ITP)is an acquired disease characterized by isolated thrombocytopenia,which is one of the most common causes of thrombocytopenia during pregnancy.Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications.Therefore,we established this consensus statement on the diagnosis and management of ITP during pregnancy(detailed information is available in the Supplementary File,http://links.lww.com7CM9/A978).