Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance to apoptosis has been described in neutrophils from patients with PNH and related hematologic disorders (aplastic anemia, myelodysplastic syndrome), but its molecular basis is not understood. Using gene expression analysis, PNH granulocytes had relative overexpression of four anti-apoptosis genes (human A1, hHR23B, Mcl-1, and RhoA) compared to normal controls. These findings were confirmed by RT-PCR analysis and observed in both peripheral blood granulocytes and mononuclear cells of patients with PNH. Anti-apoptosis gene upregulation may confer resistance to apoptosis in PNH and related disorders, and provide a common compensatory mechanism after bone marrow injury that allows survival and growth of remaining hematopoietic stem cells.
 ...
PMID:Increased expression of anti-apoptosis genes in peripheral blood cells from patients with paroxysmal nocturnal hemoglobinuria. 1270 80

Hematopoietic differentiation is strictly regulated by complex network of transcription factors that are controlled by ligands binding to cell surface receptors. Disruptions of the intricate sequences of transcriptional activation and suppression of multiple genes cause hematological diseases, such as leukemias, myelodysplastic syndromes, or myeloproliferative syndromes. From a clinical standpoint, deciphering the pattern of gene expression during hematopoiesis may help unravel disease-specific mechanisms in hematopoietic malignancies. Herein, we describe a human in vitro hematopoietic model system where lineage-specific differentiation of CD34(+) cells was accomplished using specific cytokines. Microarray and RNAseq-based whole transcriptome and exome analysis was performed on the differentiated erythropoietic, granulopoietic, and megakaryopoietic cells to delineate changes in expression of whole transcripts and exons. Analysis on the Human 1.0 ST exon arrays indicated differential expression of 172 genes (P < 0.0000001) and significant alternate splicing of 86 genes during differentiation. Pathway analysis identified these genes to be involved in Rac/RhoA signaling, Wnt/B-catenin signaling and alanine/aspartate metabolism. Comparison of the microarray data to next generation RNAseq analysis during erythroid differentiation demonstrated a high degree of correlation in gene (R = 0.72) and exon (R = 0.62) expression. Our data provide a molecular portrait of events that regulate differentiation of hematopoietic cells. Knowledge of molecular processes by which the cells acquire their cell-specific fate would be beneficial in developing cell-based therapies for human diseases.
 ...
PMID:Transcriptome profiling and sequencing of differentiated human hematopoietic stem cells reveal lineage-specific expression and alternative splicing of genes. 2182 45

The transcriptional activity of RHOA, SEMA3B, and CKAP2 genes was assessed in blood samples of leukaemia patients and healthy donors. In the blood of healthy donors, RHOA and CKAP2 gene expression was not detected, and low SEMA3B gene expression was observed. Significant elevation of expression of all the three genes was shown in the case of acute myelogenous leukaemia. In cases of remission of acute lymphoblastic leukaemia and myelodysplastic syndrome, no expression of all three genes was detected. The long isoform of the CKAP2 gene was highly expressed in most analysed types of leukaemia.
...
PMID:RHOA, SEMA3B, and CKAP2 expression in leukaemia of different types: the results of a pilot experiment. 2428 Jan 43

A 75-year-old man with no prior history of cytotoxic therapy presented with increasing fatigue and shortness of breath. He was found to have a new onset of pancytopenia, and chest X-ray showed severe pneumonia. Additional radiology exam revealed pan-lobar pneumonia, pleural effusion, generalized lymphadenopathy and mild splenomegaly. Bone marrow and mediastinal lymph node biopsy from the bilateral level 4 lymph nodes were performed to evaluate the cause of pancytopenia and generalized lymphadenopathy, respectively. Histologic sections of lymph nodes were consistent with angioimmunoblastic T-cell lymphoma (AITL), and bone marrow biopsy showed low level involvement by AITL. Background trilineage hematopoiesis showed features suggestive of myelodysplastic syndrome (MDS) with karyotyping showing deletion 20q; however, interpretation of dysplasia and exclusion of reactive process was difficult due to the presence of severe infection, administration of multiple medications and multiorgan failure. Therefore, to further evaluate the possibility of concomitant myeloid neoplasm, we performed flow cytometry sorting of bone marrow aspirate to isolate the myeloid cell population from the abnormal T-cell population, and comprehensive genomic profiling was performed in each population separately. Flow-sorted myeloid population showed three somatic mutations involving DNMT3A and BCORL1, supporting the diagnosis of MDS in conjunction with the presence of deletion 20q. Flow sorted abnormal T-cell population showed six somatic mutations consistent with AITL, involving Ras homolog gene family member A (RHOA), TET2, DNMT3A, NOTCH2 and XPO1. These two sorted populations shared the DNMT3A p.N612Rfs*26 mutation, and the variants unique to one sorted population were confirmed to be completely absent in another sorted population by manual review of the sample. These findings suggested that the two neoplasms were clonally related and were sharing a common hematopoietic progenitor precursor, but underwent clonal divergence over time, leading to the development of two distinct neoplastic processes of T and myeloid lineages. This illustrates a rare case of concurrent diagnosis of AITL and de novo MDS and reliable genomic assessment was performed at the time of diagnosis to detect mutations in each neoplastic process without contamination. Further studies are needed to assess hypomethylating agents as potential therapy options for these patients.
 ...
PMID:Molecular Genetic Analysis With Flow Cytometry Sorting Identifies Angioimmunoblastic T-Cell Lymphoma and Concomitant De Novo Myelodysplastic Syndrome Arising From the Same Hematopoietic Progenitor. 3322 95