tretinoin and Anemia--Aplastic

Topics: Anemia, Aplastic; Antineoplastic Agents; Blood Transfusion; Bone Marrow; Bone Marrow Transplantation; Cell Differentiation; Colony-Stimulating Factors; Humans; Myelodysplastic Syndromes; Preleukemia; Prognosis; Tretinoin

Severe acquired aplastic anaemia (AA) is a serious disease characterised by autoreactive T cells attacking haematopoietic stem cells, leading to marrow hypoplasia and pancytopenia. Immunosuppressive therapy combined with antithymocyte globulin and ciclosporin can rescue most patients with AA. However, the relapse after ciclosporin withdrawal and the severe side effects of long-term ciclosporin administration remain unresolved. As such, new strategies should be developed to supplement current therapeutics and treat AA. In this study, the possibility of all-trans-retinoic acid (ATRA) as an alternative AA treatment was tested by using an immune-mediated mouse model of AA. Results revealed that ATRA inhibited T-cell proliferation, activation and effector function. It also restrained the Fas/Fasl pathway, shifted Th1 towards Th2 cell development, rebalanced T-cell subsets at a relatively high level and corrected the Th1/Th2 ratio by targeting NFAT1 signalling. In addition, ATRA inhibited Th17 cell differentiation and promoted regulatory T-cell development. Therefore, ATRA was an effective agent to improve AA treatment outcomes.

Topics: Anemia, Aplastic; Animals; Cell Differentiation; Female; Male; Mice; Mice, Inbred BALB C; NFATC Transcription Factors; Signal Transduction; Th1 Cells; Th17 Cells; Th2 Cells; Tretinoin

Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods. The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.

Topics: Adolescent; Adult; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Drug Resistance, Neoplasm; Female; Flow Cytometry; fms-Like Tyrosine Kinase 3; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Oxides; Prognosis; Proto-Oncogene Proteins c-bcl-2; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Tandem Repeat Sequences; Tretinoin; Young Adult

Topics: Adult; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Remission Induction; Tretinoin