Targeting on glycosylation of mutant FLT3 in acute myeloid leukemia.

Conclusions: The abnormal location of FLT3 caused by different glycosylation status leads to the distinguishing signaling pathways. Targeting on FLT3 glycosylation may provide a new perspective for therapeutic strategies. Abbreviations: ABCG2: ATP-binding cassette transporter breast cancer resistance protein; ATF: activating transcription factor; AML: acute myeloid leukemia; CHOP: CCAAT-enhancer-binding protein homologous protein; 2-DG: 2-deoxy-D-glucose; EFS: event free survival; EPO: erythropoietin; EPOR: erythropoietin receptor; ERS: endoplasmic reticulum stress; FLT3: FMS-like tyrosine kinase 3; GPI: glycosylphosphatidylinositol; HSP: heat shock protein; ITD: internal tandem duplication; IRE1a: inositol-requiring enzyme 1 alpha; JNK: c-Jun N-terminal kinase; JMD: juxtamembrane domain; JAK: janus kinase; MAPK/ERK: mitogen activated protein kinase/extracellular signal-regulated protein kinase; OS: overall survival; PI3K/AKT: phosphatidylinositide 3-kinases/protein kinase B; PERK: RNA-activated protein kinase-like endoplasmic reticulum kinase; Pgp: P-glycoprotein; PTX3: human pentraxin-3; STAT: signal transducer and activator of transcriptions; TKD: tyrosine-kinase domain; TKI: tyrosine kinase inhibitor; TM: Tunicamycin; UPR: unfolded protein reaction. PMID: 31533545 [PubMed - in process]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research

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This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM o...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
DOK6; Methylation; AML. AbstractBackgroundDownstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role ofDOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies ofDOK6 have not dealt with its roles in myeloid malignancies. Herein, we verified the promoter methylation status ofDOK6 and further explored its clinical implication in de novo acute myeloid leukemia (AML).MethodsA total of 100 newly diagnosed adult AML patients were involved in th...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Authors: He H, Li J, Xu M, Kan Z, Gao Y, Yuan C Abstract Septin 2 (SEPT2) is a tumor-related gene belonging to the SEPT family that affects the cellular processes of hepatoma carcinoma cells, glioblastoma cells and mesangial cells and is highly expressed in breast cancer, biliary tract cancer and acute myeloid leukemia. Colorectal cancer (CRC) is the third most common type of malignancy in humans. In the present study, Oncomine database was used to compare the expression pattern of SEPT2 mRNA between CRC and normal tissues. Additionally, protein expression in 90 pairs of CRC and paracancerous tissues was analyzed b...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Publication date: Available online 6 August 2019Source: Cancer GeneticsAuthor(s): Prasad Koduru, Weina Chen, Barbara Haley, Kevin Ho, Dwight Oliver, Kathleen WilsonAbstractBreast cancer patients treated with adjuvant chemotherapy regimens containing alkylating agents and anthracyclines are at an increased risk for secondary myeloid malignancies, either acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Complex genomic changes (karyotypes and/or gene amplification) accompany the development of the secondary neoplasms. Here we present a unique case of a breast cancer patient who developed secondary AML within 18...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
We describe here a case of AML with apparent amplification of RUNX1 by cytogenetics and FISH. A 39-year-old female in remission from stage IIIa breast cancer was diagnosed with therapy-related AML (t-AML). The patient's bone marrow was hypocellular for her age (30-40%) with 25% blasts. Cytogenetic analyses revealed a complex karyotype, characterized by rearrangements in chromosomes 1, 5, 17, 20, an additional unidentified marker chromosome, and apparent amplification of chromosome 21. Fluorescence in situ hybridization detected deletions of CKS1B, EGR1, TP53, and apparent amplification of RUNX1 (6-8 signals). Array compara...
Source: Cancer Genetics - Category: Cancer & Oncology 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
Abstract Cancer Stem Cells (CSCs) are the subpopulation of cells present in the tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. Therefore, the research work on the CSC has provided a promising approach for the improvement of cancer therapies in the future. The CSCs have a close connection with the cytokines related with the T helper 17 (Th17) cell and other factors present in the tumor microenvironment, and these play a pivotal role in tumor progression and metastasis. The properties of CSCs are well defined in various type of tumor which is main...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research
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Source: JAMA Dermatology - Category: Dermatology Source Type: research
This study, aimed to explore the role of YTHDF1 in the colorectal cancer (CRC). In this study, we identified YTHDF1 as being highly expressed at the mRNA and protein levels in TCGA, GEO CRC and primary CRC. Furthermore, the YTHDF1 gene copy number was positively correlated with YTHDF1 mRNA expression in CRC. Knocking down the expression of YTHDF1 significantly inhibited the CRC cell's tumorigenicity in vitro and murine xenograft tumor growth in vivo. Furthermore, silencing of YTHDF1 inhibited the colonosphere formation ability in vitro. Mechanistically, we found that silencing YTHDF1 significantly inhibited Wnt/&be...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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