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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV), which is associated with B-cell proliferative disorders, also transforms T- or natural killer (NK)-lineage cells and has been connected with various T- or NK (T/NK)-cell malignancies, such as extranodal NK/T-cell lymphoma-nasal type and aggressive NK-cell leukemia. Chronic active EBV (CAEBV) disease , which occurs most often in children and young adults in East Asia, is an EBV-associated T-/NK-cell lymphoproliferative disease. Patients with CAEBV often progress to overt lymphoma or leukemia over a long-term clinical course. EBV's transforming capacity in B cells is well characterized, but the molecular pathogenesis of clonal expansion caused by EBV in T/NK cells has not yet been clarified. In the primary infection, EBV infects B cells and epithelial cells and may also infect some T/NK cells. In some individuals, because of poor presentation by specific human leukocyte antigens or the genetic background, EBV-infected T/NK cells evade host immunity and survive. Occasionally, with the help of viral oncogenes, EBV-associated T/NK lymphoproliferative diseases, such as CAEBV, may develop. The subsequent accumulation of genetic mutations and/or epigenetic modifications in driver genes, such as DDX3X and TP53, may lead to overt lymphoma and leukemia. Activation-induced cytidine deaminase and the APOBEC3 family, driven by EBV infection, may induce chromosomal recombination and somatic mutations.
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PMID:EBV in T-/NK-Cell Tumorigenesis. 2989 80

Large granular lymphocyte leukemia (LGL) are chronic lymphoproliferative disorders classified into three main groups: T-cell LGL leukemia (T-LGL), aggressive NK-cell leukemia and chronic lymphoproliferative disorder of NK cells (NK-LGL). Patients with LGL leukemia exhibit chronic (>3 months) and moderate (<1G/L) to substantial monoclonal expansion of large granular lymphocytes in the peripheral blood. Cytologically, large granular lymphocytes are medium to large cells which are further characterized by an eccentric nucleus and a slightly basophilic cytoplasm containing azurophilic granules. Typically, T-LGL (CD3-and mostly CD8+) can be differentiated from NK-LGL disorders (CD3-) based on flow cytometry analysis. However, distinction between LGL leukemias can be tricky. We report here the case of a 47-year-old woman patient diagnosed with large granular lymphocytes leukemia associated with atypical CD3-CD56- immunophenotyping and clinical manifestations of pseudo-Felty's syndrome.
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PMID:Large granular lymphocytic leukemia CD3-CD56-: a challenge for the biologist and the physician. 3007 79

Leukemia is a group of hematologic malignancy that has unfavorable prognosis and unclear mechanisms. In recent years, advances in leukemia research encompass the discovery of novel targets in acute myeloid leukemia drug resistance, epigenetic crosstalk in mixed lineage leukemia (MLL) leukemogenesis, genetic mechanisms of aggressive NK-cell leukemia, as well as the critical role of key epigenetic regulator in acute myeloid malignancy. Remarkably, researchers revealed that the histone modifying gene SETD2 as a new tumor suppressor and therapeutic target in patients with acute myeloid leukemia. Furthermore, low-dose chemotherapy as a frontline regiment in treating pediatric acute myeloid leukemia can substantially reduce the toxic side effects and treatment costs without impairing efficacy. Although advances in cancer genomics have greatly increased our understanding of the molecular characteristics in tumor biology, recent studies suggest that Darwinian evolution of intratumor heterogeneity represents a major challenge to develop therapeutic strategies to improve disease control. Researchers also dissected the distinct evolutionary dynamics under different chemotherapy regimens and the corresponding applications in the evaluation of treatment outcomes. Altogether, these efforts offered new opportunities for the development of acute myeloid leukemia diagnostics and therapeutics.
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PMID:[Precision genomic and translational medicine for acute myeloid leukemia]. 3046 31

Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas [33 (22%) of 148 cases], including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%). Predominantly causing a truncation of the 3'-untranslated region, these alterations represented the most prevalent somatic lesions in ENKTL. By contrast, the frequency was much lower in EBV-negative lymphomas regardless of histology type [12 (5%) of 236 cases]. Besides PD-L1/PD-L2 alterations, EBV-positive DLBCL exhibited a genetic profile distinct from EBV-negative one, characterized by frequent TET2 and DNMT3A mutations and the paucity of CD79B, MYD88, CDKN2A, and FAS alterations. Our findings illustrate unique genetic features of EBV-associated lymphomas, also suggesting a potential role of detecting PD-L1/PD-L2-involving lesions for these lymphomas to be effectively targeted by immune checkpoint blockade.
Leukemia 2019 07
PMID:Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. 3068 10

Introduction: Natural killer (NK)/T-cell lymphomas are aggressive malignancies that present predominantly in nasal and adjacent sites (nasal subtype), occasionally in skin, gastrointestinal tract and other tissues (non-nasal), and rarely as disseminated disease with a leukemic phase (aggressive NK-cell leukemia, or leukemia/lymphoma, subtype).Areas covered: The diagnosis and treatment of NK/T-cell lymphoma are discussed, based on a PubMed literature search. The diagnostic criteria for NK/T-cell lymphoma are highlighted, followed by an update of the diagnostic and prognostic importance (on presentation, at interim and end-of-treatment) of plasma EBV DNA as a surrogate biomarker of lymphoma load. Prognostic models based on clinicopathologic features and EBV DNA load are discussed. For stage I/II NK/T-cell lymphomas, combined chemotherapy, and radiotherapy gives the best results, with their concomitant or sequential administration equally efficacious. For stage III/IV NK/T-cell lymphoma, chemotherapy is the mainstay of treatment. Conventional anthracycline-based regimens for B-cell lymphomas are ineffective. Recommended regimens combine L-asparaginase with other drugs not affected by P-glycoprotein. For relapsed/refractory patients, immune checkpoint blockade with antibodies against programmed cell death protein 1 has shown much promise.Expert opinion: Current strategies result in durable remissions in a significant proportion of NK/T-cell lymphomas. Immune checkpoint inhibition and other novel approaches are promising for relapsed/refractory cases.
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PMID:Recent advances in the diagnosis and treatment of natural killer/T-cell lymphomas. 3148 2


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