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39


Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of Cutaneous T Cell Lymphoma

Fanok, Melania H; Sun, Amy; Fogli, Laura K; Narendran, Vijay; Eckstein, Miriam; Kannan, Kasthuri; Dolgalev, Igor; Lazaris, Charalampos; Heguy, Adriana; Laird, Mary E; Sundrud, Mark S; Liu, Cynthia; Kutok, Jeff; Lacruz, Rodrigo S; Latkowski, Jo-Ann; Aifantis, Iannis; Odum, Niels; Hymes, Kenneth B; Goel, Swati; Koralov, Sergei B
Cutaneous T cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome revealed a highly heterogeneous landscape of genetic perturbations and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway, previously implicated in CTCL pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of CTCL. Using this mouse model, we demonstrate that T cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.
PMCID:5912980
PMID: 29128259
ISSN: 1523-1747
CID: 2785082

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Bustoros, Mark; Liechty, Benjamin; Zagzag, David; Liu, Cynthia; Shepherd, Timothy; Gruber, Deborah; Raphael, Bruce; Placantonakis, Dimitris G
Background/UNASSIGNED:Primary extranodal marginal zone lymphoma (MZL) of the dura is a rare neoplastic entity in the central nervous system (CNS). Methods/UNASSIGNED:We used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Results/UNASSIGNED:We identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes. Conclusion/UNASSIGNED:Primary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.
PMCID:5928293
PMID: 29740389
ISSN: 1664-2295
CID: 3085002

TET1 is a tumor suppressor of hematopoietic malignancy

Cimmino, Luisa; Dawlaty, Meelad M; Ndiaye-Lobry, Delphine; Yap, Yoon Sing; Bakogianni, Sofia; Yu, Yiting; Bhattacharyya, Sanchari; Shaknovich, Rita; Geng, Huimin; Lobry, Camille; Mullenders, Jasper; King, Bryan; Trimarchi, Thomas; Aranda-Orgilles, Beatriz; Liu, Cynthia; Shen, Steven; Verma, Amit K; Jaenisch, Rudolf; Aifantis, Iannis
The methylcytosine dioxygenase TET1 ('ten-eleven translocation 1') is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.
PMCID:4545281
PMID: 25867473
ISSN: 1529-2916
CID: 1532762

Limited miR-17-92 overexpression drives hematologic malignancies

Danielson, Laura S; Reavie, Linsey; Coussens, Marc; Davalos, Veronica; Castillo-Martin, Mireia; Guijarro, Maria V; Coffre, Maryaline; Cordon-Cardo, Carlos; Aifantis, Iannis; Ibrahim, Sherif; Liu, Cynthia; Koralov, Sergei B; Hernando, Eva
The overexpression of microRNA cluster miR-17-92 has been implicated in development of solid tumors and hematological malignancies. The role of miR-17-92 in lymphomagenesis has been extensively investigated; however, because of the developmental defects caused by miR-17-92 dysregulation, its ability to drive tumorigenesis has remained undetermined until recently. Here we demonstrate that overexpression of miR-17-92 in a limited number of hematopoietic cells is sufficient to cause B cell malignancies. In sum, our study provides a novel and physiologically relevant model that exposes the potent ability of miR-17-92 to act as a driver of tumorigenesis.
PMCID:4376677
PMID: 25597017
ISSN: 0145-2126
CID: 1439872

Synchronous Gastric and Diffuse Colonic MALT Lymphoma in a Patient With Strongyliodes Infection: A Causal or Incidental Association [Meeting Abstract]

Subei, Obada; Zahir, Ismail; Liu, Cynthia; Gandhi, Soren
ISI:000363715900323
ISSN: 1572-0241
CID: 1854252

Expression of c-MYC and MMP9 in Alternatively Activated Macrophages (M2) of Classical Hodgkin Lymphoma [Meeting Abstract]

Yang, Long; Harris, Jonathan A; Ibrahim, Sherif; Liu, Cynthia
ISI:000349233802204
ISSN: 1528-0020
CID: 1497532

Extranodal natural killer/T-cell lymphoma masquerading as conjunctivitis [Letter]

Charles, Norman C; Liu, Cynthia Z; Belinsky, Irina; Patel, Payal
PMID: 25103666
ISSN: 0008-4182
CID: 1252272

A JAK2-V617F mutation patient developed Philadelphia positive CML/AP - a case report [Meeting Abstract]

Liu, C.; Amorosi, E.; Ibrahim, S.
ISI:000308126900346
ISSN: 0309-0167
CID: 178292

C-kit (CD117) expression in mucosal melanomas of head and neck-42 cases of eastern Chinese patients [Meeting Abstract]

Chen, G.; Wu, L.; Li, P.; Kong, M. X.; Liu, C.; Sun, W.; Wang, B. Y.
ISI:000308126900424
ISSN: 0309-0167
CID: 178291

CD163 versus CD68 in tumor associated macrophages of classical hodgkin lymphoma

Harris, Jonathan A; Jain, Salvia; Ren, Qinghu; Zarineh, Alirezah; Liu, Cynthia; Ibrahim, Sherif
ABSTRACT: Classical Hodgkin lymphoma (CHL) is a B-cell lymphoproliferative disorder with a relatively good prognosis. A small but significant percentage of patients, however, will respond poorly to therapy. A recent gene expression profiling study has identified a macrophage signature which has been correlated with primary treatment failure, and immunohistochemical tissue microarray for CD68 was shown to reflect the gene signature as a potentially clinically useful marker to predict adverse prognosis.We examined 44 cases of CHL, mostly nodular sclerosis subtype, in which the immunohistochemical stains for the histiocytic markers CD68 and CD163 were performed. The staining intensity was graded for each stain (< 5, 5-25, and > 25 percent of cells positive in the Hodgkin cell (HC) rich nodules) and background staining characteristics were recorded.CD163 staining was lower than CD68 in HC rich nodules, with lower background staining (p 0.03). There was no significant difference between either CD68 or CD163 and disease recurrence in a subset (N = 41) of cases.In conclusion, we demonstrate that CD163 staining is lower than CD68, with less non-specific staining of background inflammatory cells and Hodgkin cells, therefore is a better marker for tumor associated macrophages. However, we did not identify a correlation between staining for CD68 or CD163 and recurrence of disease. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1460518258831620.
PMCID:3281786
PMID: 22289504
ISSN: 1746-1596
CID: 157482