Objective To performed microarray-based comparative genomic hybridization (aCGH) detection and carried out pathway analysis to gain a systemic view on the pathway alterations of the genetically altered genes in human osteosarcoma.Methods aCGH experiments were carried on 10 fresh osteosarcoma samples to obtain recurrent copy number change pattern,then the samples were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify the altered pathways in the osteosarcoma.To validate the aberrations of these key pathways,the alterations of VEGF pathway were selected to confirm by the methods of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) osteosarcoma archival tissues.Results The KEEG analysis of aCGH data identified 33 genetically altered pathways in osteosarcomas.Among them 20 pathways were identified genetic amplifications,such as VEGF and mTOR signaling pathways.Thirteen pathways were genetic deletions,such as Wnt and Hedgehog signaling pathways.The genetic aberrations of cell-cell-matrix pathway such as CAMs,Adherens junction and Tight junction pathways implied the genetically alterations of these pathways which are associated with the tumor invasion and metastasis.Validation the aberrations of VEGF pathway showed that VEGFA gene was significantly amplified.The positive protein expression of VEGFA had a significant association with microvessel density (MVD).Conclusion There are genetic aberrations which involved the component genes of VEGF,mTOR,CAMs,Adherens junction,Wnt,Hedgehog and other 26 signaling pathways.The alterations of these pathways which are significantly associated with tumor invasion,metastasis and progression suggest that the genetic aberrations of these key pathways might contribute to the tumorigenesis and progression in human osteosarcoma,and provide molecular genetic evidence for targeted therapy.

Objective:To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion.Methods:The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up.Results:The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %.Conclusions:TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.