Fenretinide-induced Apoptosis of Acute Myeloid Leukemia Cells via NR4A1 Translocation into Mitochondria and Bcl-2 Transformation

CONCLUSIONS: Fenretinide exerts an obvious effect on AML cells both in vitro and in vivo. Besides, the NR4A1-mediated signaling pathway is highly involved in the fenretinide-induced apoptosis of AML cells.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research

Related Links:

i Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-ΣMMHX) translocation product respectively, disrupt the essential hematopoie...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
rlach Sabattini Testoni Iacobucci Huntly Ficarra Martinelli Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification of these rare chimeras is of interest to characterize AML patients. Here, we studied the transcriptome of 8 adult AML patients with poorly described chromosomal translocation(s), with the aim of identifying novel and rare fusion transcripts. We integrated RNA-sequencing data with multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization and i...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 17 October 2019Source: Stem Cell ResearchAuthor(s): Amanda E. Yamasaki, Nicholas E. King, Hiroko Matsui, Kristen Jepsen, Athanasia D. PanopoulosAbstractUsing iPSCs to study cancer has been complicated by the fact that many cancer cells are difficult to reprogram, which has been attributed to the genomic abnormalities present. Acute Myeloid Leukemia (AML) is a complex disease that presents with various types of genomic aberrations that affect prognosis. Here we reprogrammed CD34+ cells from an AML patient containing a rare der(7)t(7;13) translocation associated with poor prognosis, who had...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
n Emadi Acute myeloid leukemia (AML) is a neoplastic disorder resulting from clonal proliferation of poorly differentiated immature myeloid cells. Distinct genetic and epigenetic aberrations are key features of AML that account for its variable response to standard therapy. Irrespective of their oncogenic mutations, AML cells produce elevated levels of reactive oxygen species (ROS). They also alter expression and activity of antioxidant enzymes to promote cell proliferation and survival. Subsequently, selective targeting of redox homeostasis in a molecularly heterogeneous disease, such as AML, has been an appealing app...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Publication date: Available online 23 August 2019Source: Cancer GeneticsAuthor(s): Chun Hang Au, Dona N. Ho, Beca B.K. Ip, Thomas S.K. Wan, Margaret H.L. Ng, Edmond K.W. Chiu, Tsun Leung Chan, Edmond S.K. MaAbstractDetection of chromosomal translocation is a key component in diagnosis and management of acute myeloid leukemia (AML). Targeted RNA next-generation sequencing (NGS) is emerging as a powerful and clinically practical tool, but it depends on expression of RNA transcript from the underlying DNA translocation. Here, we show the clinical utility of nanopore long-read sequencing in rapidly detecting DNA translocation ...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
Abstract Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the BCR-FGFR1 fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-Cell lymphoma. This work focuses on biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, IL-3 independe...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Somatic perturbations such as translocation, mutation, deletion, gene amplification and epigenetic modification in proto-oncogenes and/or tumor suppressor genes may result in unscheduled expression of proto-oncogenes, or altered function of tumor suppressor genes, or cause gene overexpression in tumors. Gene amplification is a unique form of genomic instability in cancer genome and is often considered a biomarker for aggressive disease that is resistant to therapy. While low level amplification is represented by copy number gains (trisomy or tetrasomy), high level amplification may manifest morphologically as a homogeneous...
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Tags: Case Report Source Type: research
Human cancer cells operate a variety of effective molecular and signalling mechanisms which allow them to escape host immune surveillance and thus progress the disease. We have recently reported that the immune receptor Tim-3 and its natural ligand galectin-9 are involved in the immune escape of human acute myeloid leukaemia cells. These cells use the neuronal receptor latrophilin 1 (LPHN1) and its ligand fibronectin leucine rich transmembrane protein 3 (FLRT3, and possibly other ligands) to trigger the pathway. We hypothesised that the Tim-3-galectin-9 pathway may be involved in the immune escape of cancer cells of differ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 12 June 2019Source: Cancer GeneticsAuthor(s): D. Tolomeo, A. L'Abbate, A. Lonoce, P. D'Addabbo, M.F. Miccoli, C. Lo Cunsolo, P. Iuzzolino, O. Palumbo, M. Carella, V. Racanelli, T. Mazza, E. Ottaviani, G. Martinelli, G. Macchia, C.T. StorlazziAbstractAcute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous hematological disorder defined by morphological, genetic, and clinical features. Patients with AML-MRC often show cytogenetic changes, which are associated with poor prognosis. Straightforward criteria for AML-MRC diagnosis and a more rigorous characterizat...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Cancer | Cancer & Oncology | Leukemia | Mitochondria | Study | Translocation