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Leukemia, Myelomonocytic, ChronicLeukemia, Myelomonocytic, AcuteLeukemiaLeukemia, Myelomonocytic, JuvenileCell DifferentiationMyeloid-Lymphoid Leukemia ProteinLeukemia, MyeloidLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaAntigensAcute DiseaseProto-OncogenesAntigens, SurfaceLeukemia, Monocytic, AcuteTranslocation, GeneticGene Expression Regulation, LeukemicAntigens, NeoplasmLeukemia, LymphoidAntigens, BacterialChromosomes, Human, Pair 11Bone MarrowLeukemia, Biphenotypic, AcuteOncogene Proteins, FusionGene RearrangementTranscription FactorsCell LineAntigens, CDHematopoietic Stem CellsLeukemia, ExperimentalMolecular Sequence DataTumor Cells, CulturedMyelodysplastic SyndromesImmunophenotypingHL-60 CellsDNA-Binding ProteinsBase SequenceCells, CulturedAntigens, ViralDual Specificity Phosphatase 2Flow CytometryBone Marrow CellsRNA, MessengerNeoplasm ProteinsCore Binding Factor Alpha 2 SubunitBlast CrisisCell DivisionLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMonocytesArabinonucleosidesCell Transformation, NeoplasticProto-Oncogene ProteinsT-LymphocytesKaryotypingB-LymphocytesCytarabineAntibodies, MonoclonalNeoplastic Stem Cellsfms-Like Tyrosine Kinase 3MutationHematopoiesisAntigens, Differentiation, MyelomonocyticLeukemia-Lymphoma, Adult T-CellChromosomes, Human, Pair 4Signal TransductionOncogene Proteins v-mybAntigens, DifferentiationGranulocytesAmino Acid SequenceStem CellsChromosome AberrationsGene Expression RegulationMice, Inbred C57BLReverse Transcriptase Polymerase Chain ReactionCell LineageAntineoplastic AgentsHLA AntigensTretinoinNuclear ProteinsAntigens, ProtozoanApoptosisMyeloproliferative DisordersBurkitt LymphomaPhenotypePolymerase Chain ReactionHomeodomain ProteinsChromosome DisordersTranscription, GeneticAntigens, Polyomavirus TransformingCell ProliferationDNA, NeoplasmGene ExpressionRecombinant Fusion ProteinsFluorescent Antibody TechniqueGene Expression Regulation, DevelopmentalLeukemia, Promyelocytic, AcuteHistone-Lysine N-MethyltransferaseCell Line, TumorMice, Inbred BALB CU937 CellsAntigens, Fungal
MalignanciesNeoplasmProgressionLeukaemiaLymphoidChronicMutationsProliferationMyelogenous leukemiaHematopoietic stemMyelodysplastic syndromeLineageTransformationPromyelocyticMonocytesPathogenesisGenesFlow cytometryPoor prognosisCellsNeoplasticStem cellMonocyticPatientsReceptorOncogenicPrognosticProfilingChromatinLesionsHeterogeneousDiagnosisCollectivelyGene expressionGenetic alterationsFrontiersChemotherapyClassificationMaturationLaboratoryBone
Malignancies5
  • [ 1 , 2 , 3 ] Owing to the variety of hematologic malignancies or proliferative disorders that may be associated with leukemia cutis, terms such as myeloid or lymphoid leukemia cutis have been used to further classify the leukemic cells. (medscape.com)
  • The present study demonstrated the biological and functional evidence for the critical role of RUNX1 -MT in ASXL1 -mutated leukemia in the pathogenesis of myeloid malignancies. (biomedcentral.com)
  • The presence of the characteristic chromosomal translocation always involving the fibroblast growth factor receptor 1 ( FGFR1 ) gene at chromosome 8p11 in both the myeloid and lymphoid malignancies suggests bilineage differentiation from an affected pluripotent stem cell. (medscape.com)
  • Dysregulation of this process has been associated with aberrant gene expression and function, leading to hematopoietic malignancies. (bvsalud.org)
  • U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. (cancer-genetics.org)
Neoplasm2
  • This work builds on existing knowledge that PDCs can be divided into two categories: mature PDC proliferations which result in myeloid neoplasms (MPDMN) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). (news-medical.net)
  • CCDC88C-FLT3 gene fusion in CD34-positive haematopoietic stem and multilineage cells in myeloid/lymphoid neoplasm with eosinophilia. (u-tokyo-hemat.com)
Progression3
  • These lead to progression of acute myeloid leukemia. (medscape.com)
  • A heterogenous group of myeloid disorders characterized by somatically mutated hematopoietic stem cells,the presence of variable peripheral cytopenias, and a broad risk of progression to acute myeloid leukemia (AML). (standardofcare.com)
  • In melanoma, i have focused in acral lentiginous melanoma for which we described KIT mutation and protein expression status in a large series of cases and described TERT amplification in progression to metastasis. (mdanderson.org)
Leukaemia2
Lymphoid2
Chronic10
  • In the setting of chronic leukemia, cutaneous involvement can indicate blast transformation. (medscape.com)
  • Additional sex combs-like 1 ( ASXL1 ) mutations have been described in all forms of myeloid neoplasms including chronic myelomonocytic leukemia (CMML) and associated with inferior outcomes, yet the molecular pathogenesis of ASXL1 mutations ( ASXL1 -MT) remains poorly understood. (biomedcentral.com)
  • Previously, we observed that transcription factor RUNX1 mutations ( RUNX1 -MT) coexisted with ASXL1 -MT in CMML and at myeloid blast phase of chronic myeloid leukemia. (biomedcentral.com)
  • We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1 MT in chronic myelomonocytic leukemia (CMML). (nature.com)
  • Chronic myeloid neoplasms are malignant clonal hematopoietic stem cell disorders driven by recurrent genetic events, with an inherent risk of transformation to acute myeloid leukemia (AML) 1 , 2 . (nature.com)
  • Within myeloid neoplasms, chronic myelomonocytic leukemia (CMML) represents an attractive disease model since it is characterized by both myelodysplastic and myeloproliferative features, while retaining a relatively simple clonal composition 3 . (nature.com)
  • As with chronic myelogenous leukemia (CML) , the myeloproliferative aspect of SCLL has a chronic phase that transforms into a myeloblastic phase, typically within 1 year of diagnosis. (medscape.com)
  • Findings consistent with chronic myelomonocytic leukemia have been noted in at least several patients. (medscape.com)
  • Classical Hairy Cell Leukemia (HCL) and HCL-like disorders are a very heterogeneous group of mature B-cell Chronic Lympho proliferative Disorders (B-CLPD). (fortuneonline.org)
  • Collectively, mutations in U2AF1 induce expression of therapeutically targetable 'active' IRAK4 isoforms and provide a genetic link to activation of chronic innate immune signalling in MDS and AML. (cancer-genetics.org)
Mutations8
  • Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). (ox.ac.uk)
  • Class II mutations cause defects in myeloid cell differentiation. (medscape.com)
  • The contribution of RUNX1 mutations in the pathogenesis of myeloid transformation in ASXL1 -mutated leukemia, however, remains unclear. (biomedcentral.com)
  • Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of RUNX1 and ASXL1 mutations played a critical role in leukemia transformation. (biomedcentral.com)
  • Mice transduced with both ASXL1 and RUNX1 mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. (biomedcentral.com)
  • CMML shares the typical repertoire of genetic driver lesions with other myeloid neoplasms and is particularly enriched in truncating mutations involving ASXL1 (prevalence ~40%) 3 . (nature.com)
  • Through recent clinical and mouse model analyses, insights have been gained into the mechanisms underlying splicing factor mutations that aid in myelodysplastic syndrome and acute myeloid leukemia. (bvsalud.org)
  • Scope includes mutations and abnormal protein expression. (cancer-genetics.org)
Proliferation8
  • However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. (ox.ac.uk)
  • Accumulation of genetic defects in hematopoietic precursors leads to impaired cellular differentiation, increased proliferative potential, unregulated proliferation, and defective apoptosis. (medscape.com)
  • To evaluate the leukemogenic role of RUNX1-MT in ASXL1 -mutated cells, we co-expressed RUNX1 -MT (R135T) and ASXL1 -MT (R693X) in different cell lines and performed immunoblot, co-immunoprecipitation, gene expression microarray, quantitative RT-PCR, cell proliferation, differentiation, and clonogenic assays for in vitro functional analyses. (biomedcentral.com)
  • The expression of RUNX1 mutant in ASXL1 -mutated myeloid cells augmented proliferation, blocked differentiation, and increased self-renewal activity. (biomedcentral.com)
  • The degree of methylation affects the expression of target genes and has a significant impact on cell proliferation, apoptosis, cytokine secretion, and cell activity ( 6 , 7 ). (frontiersin.org)
  • There is clonal proliferation of malignant hematopoietic stem cells, dysregulated cellular differentiation, and compromised tissue function. (standardofcare.com)
  • Acute myeloid leukemia (AML) results from the over-proliferation of progenitor cells of the myeloid lineage in the bone marrow. (ghrnet.org)
  • Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. (stanford.edu)
Myelogenous leukemia1
Hematopoietic stem1
  • Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. (nature.com)
Myelodysplastic syndrome1
  • Leukemia cutis usually occurs in the setting of a previously diagnosed systemic leukemia or lymphoproliferative disorder/myelodysplastic syndrome. (medscape.com)
Lineage3
  • The subtype of leukemia is determined by the hematopoietic lineage of neoplastic cells and the stage at which maturational arrest occurs. (medscape.com)
  • Beck's team further determined that the differentiation of PDC's may occur in the presence of monocytic or myeloid DC differentiation, or as a differentiation lineage possessing a predominant myoblast population. (news-medical.net)
  • Flow cytometric detection of intracellular antigens has become a standard method in establishing proper leukemic cell lineage affiliation. (ijpmonline.org)
Transformation2
  • Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)
  • We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. (stanford.edu)
Promyelocytic3
  • The association of t(15,17) with the M3 subtype of acute myeloid leukemia (acute promyelocytic leukemia) is one example. (medscape.com)
  • Prompt Initiation of Conventional Chemotherapy to Avoid Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia. (u-tokyo-hemat.com)
  • In Section III, Dr. Martin Tallman describes the evaluation and management of patients with acute promyelocytic leukemia, a notable example of therapeutic progress in a molecularly defined entity of leukemia. (ashpublications.org)
Monocytes1
Pathogenesis2
  • The pathogenesis of leukemia is well-characterized in the two-hit hypothesis of acute myeloid leukemia. (medscape.com)
  • In addition to these basic issues concerning leukemia pathogenesis, we are devising new diagnostic procedures for detecting and monitoring leukemia patients based on molecular genetic abnormalities in the malignant cells. (stanford.edu)
Genes2
  • Chromatin remodeling of promoters and enhancers is strongly associated with gene expression and heterogenous among overexpressed genes. (nature.com)
  • This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
Flow cytometry1
Poor prognosis2
  • A diagnosis of leukemia cutis in the setting of acute leukemia generally portends a poor prognosis and strongly correlates with additional sites of extramedullary involvement. (medscape.com)
  • DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. (frontiersin.org)
Cells21
  • Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. (ox.ac.uk)
  • p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. (ox.ac.uk)
  • Leukemia cutis is defined by migration of leukemic cells to the skin. (medscape.com)
  • The pathophysiology underlying the specific migration of leukemic cells to the skin is not clear. (medscape.com)
  • PDCs are a class of specialized dendritic cells that play a role in immunomodulatory functions and antigen presentation. (news-medical.net)
  • Both categories of cells resulting from atypical PDC differentiation are thought to represent two ends of a spectrum of maturation. (news-medical.net)
  • Moreover, the RUNX1 mutant protein was more stable than WT and increased HIF1-α and its target ID1 gene expression in ASXL1 mutant cells. (biomedcentral.com)
  • Myeloid-related precursor neoplasms derive from precursor cells that have at least one form of myeloid differentiation. (medscape.com)
  • and myeloid cells are seen in stem cell leukemia/lymphoma (SCLL), which is also known as 8p11 myeloproliferative syndrome (EMS). (medscape.com)
  • After the co-culture, the increase in pro-inflammatory cytokine expression in the mutant cells was significantly lower than that in the control group, while that in immunosuppressive factors was not significantly different. (frontiersin.org)
  • Resistin significantly promoted the expression of inflammatory proteins in AML cells. (frontiersin.org)
  • In large cell lymphoma and leukemia cells involvement of body fluid this concept becomes less challenging. (cytojournal.com)
  • Large cell lymphoma and leukemia cells tend to have large size nuclei, less mature chromatin, and visible nucleoli with and without cytoplasmic vacuoles. (cytojournal.com)
  • Aberrant expression of a third marker such as Thy-1/CD90 negativity, expression of CLL-1 and IL-3R (CD123), intermediate levels of aldehyde dehydrogenase and co-expression of common chromosomal translocation may be used to distinguish from normal hematopoietic stem cells. (ghrnet.org)
  • The diagnosis of Hairy Cell Leukemia and HCL-like diosrders, including HCL variant (vHCL) and Splenic Diffuse Red Pulp Lymphoma (SDRPL), is based on the examination of the peripheral blood and bone marrow smears allowing the identification of hairy cells and the flow cytometric analysis. (fortuneonline.org)
  • 3) We are defining the properties of cancer stem cells that initiate and sustain the unique disease features of acute leukemias through the use of various adoptive animal models. (stanford.edu)
  • Combination of analysis of fluorescence labeling and light scatter properties of cells allows rapid and better determination of target cell antigens. (ijpmonline.org)
  • Interestingly, chemotherapy, including hydroxyurea, has been associated with acute leukemia in JAK2 V617F-negative stem cells in some PV patients. (basicmedicalkey.com)
  • His pioneering work spans discoveries in basic biology of blood stem cells and leukemia to first-in-human clinical trials for people with cancer and heart diseases, alongside shaping innovative policies in state health and healthcare financing. (ufl.edu)
  • Inhibition of IRAK4-L abrogates leukaemic growth, particularly in AML cells with higher expression of the IRAK4-L isoform. (cancer-genetics.org)
  • Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)
Neoplastic1
  • Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions. (medscape.com)
Stem cell1
  • Stem cell leukemia/lymphoma (SCLL), which is also known as the 8p11 myeloproliferative syndrome (EMS), is characterized in its typical form by the occurrence, either simultaneously or sequentially, of a bcr/abl-negative myeloproliferative disorder and a lymphoma, usually a precursor T-cell lymphoblastic lymphoma. (medscape.com)
Monocytic1
  • PDC progenitors are in common with monocytic and myeloid cell progenitors. (news-medical.net)
Patients5
  • The groups study present evidence of myeloid neoplasms derived from patients with acute leukemias which encompass a spectrum of PDC differentiation which result in outcomes that do not fit into the categories of MPD MN or BPDCN. (news-medical.net)
  • Five of these patients presented with acute myeloid leukemia, one patient suffered from unclassified MN and the final patient presented with a mixed phenotype (MPAL). (news-medical.net)
  • Patients with myelodysplastic syndromes (MDS) collectively have a high symptom burden and are also at risk of death from complications of cytopenias and acute myeloid leukemia. (standardofcare.com)
  • Although the incidence of acute nonlymphocytic leukemia is increased in PV, the incidence of acute leukemia in patients not exposed to chemotherapy or radiation therapy is low. (basicmedicalkey.com)
  • In patients, primary or acquired resistance to chemotherapy is associated with the expression of P-gp. (ashpublications.org)
Receptor1
  • We show that the mH2A1 splicing isoform mH2A1.1 accumulates in MDS-MSCs, correlating with the expression of the Toll-like receptor 4 (TLR4), an important pro-tumor activator of MSC phenotype associated to a pro-inflammatory behavior. (bvsalud.org)
Oncogenic1
  • Expression of IRAK4-L is mediated by mutant U2 small nuclear RNA auxiliary factor 1 (U2AF1) and is associated with oncogenic signalling in MDS and AML. (cancer-genetics.org)
Prognostic1
  • Accurate diagnosis has tremendous prognostic significance and may establish a diagnosis in cases in which leukemia cutis is the harbinger of a systemic leukemic process. (medscape.com)
Profiling1
  • Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML. (ox.ac.uk)
Chromatin1
  • 2) We have discovered a group of oncoproteins that are implicated in long-term maintenance of gene expression through their effects on the state of chromatin. (stanford.edu)
Lesions1
Heterogeneous1
  • Acute myeloid leukemia (AML) is a common, heterogeneous, and aggressive hematopoietic malignancy, characterized by apparent genetic abnormalities ( 1 ). (frontiersin.org)
Diagnosis1
Collectively1
  • The term acute myeloid leukemia (AML) collectively refers to a mixture of distinct diseases that differ with regard to their pathogenetic evolution, genetic abnormalities, clinical features, response to therapy, and prognosis. (ashpublications.org)
Gene expression2
Genetic alterations1
Frontiers1
  • The therapeutic approach to the patient with acute myeloid leukemia (AML) currently evolves toward new frontiers. (ashpublications.org)
Chemotherapy1
Classification1
  • The group found variable expression of CD34 and CD123 in four of the cases which distinguished them from the MPDMN classification. (news-medical.net)
Maturation1
  • described three stages of PDC maturation made according to decreasing CD34 expression and increasing expression of CD123, CD303, and CD304. (news-medical.net)
Laboratory1
  • In his mid career, as a Leukemia & Lymphoma Society Scholar in Clinical Research, he translated laboratory research discoveries into investigator-initiated clinical trials. (ufl.edu)
Bone1