Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 9 of 9
Full-Text Articles in Entire DC Network
Systematic Analysis Of Hematopoietic Gene Expression Profiles For Prognostic Prediction In Acute Myeloid Leukemia, Frederick S. Varn, Erik H. Andrews, Chao Cheng
Systematic Analysis Of Hematopoietic Gene Expression Profiles For Prognostic Prediction In Acute Myeloid Leukemia, Frederick S. Varn, Erik H. Andrews, Chao Cheng
Dartmouth Scholarship
Acute myeloid leukemia (AML) is a hematopoietic disorder initiated by the leukemogenic transformation of myeloid cells into leukemia stem cells (LSCs). Preexisting gene expression programs in LSCs can be used to assess their transcriptional similarity to hematopoietic cell types. While this relationship has previously been examined on a small scale, an analysis that systematically investigates this relationship throughout the hematopoietic hierarchy has yet to be implemented. We developed an integrative approach to assess the similarity between AML patient tumor profiles and a collection of 232 murine hematopoietic gene expression profiles compiled by the Immunological Genome Project. The resulting lineage similarity …
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Dartmouth Scholarship
C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized …
Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst
Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst
Dartmouth Scholarship
HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …
Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole
Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole
Dartmouth Scholarship
No abstract provided.
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Dartmouth Scholarship
All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …
Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper
Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper
Dartmouth Scholarship
Protective immunity against Toxoplasma gondii is mediated by the host cellular immune response. Interleukin-12 (IL-12), a recently described cytokine that stimulates NK cells to produce gamma interferon (IFN-gamma), is able to enhance host protection against this parasite in SCID mice. Administration of IL-12 to A/J mice significantly increased survival over that of control mice when IL-12 was delivered early in the course of acute infection. If it was administered at day 3 or thereafter, there was no observed difference in mortality between treated and control mice. Antibody depletion of IL-12 increased susceptibility to infection, as measured by mortality, only when …
Heterogeneity Of Clonogenic Cells In Acute Myeloblastic Leukemia., Kert D. Sabbath, Edward D. Ball, Peter Larcom, Roger B. Davis, James D. Griffin
Heterogeneity Of Clonogenic Cells In Acute Myeloblastic Leukemia., Kert D. Sabbath, Edward D. Ball, Peter Larcom, Roger B. Davis, James D. Griffin
Dartmouth Scholarship
The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. …
Gamma Interferon Induces Monocytoid Differentiation In The Hl-60 Cell Line., Edward D. Ball, Paul M. Guyre, Li Shen, John M. Glynn, Charles R. Maliszewski, Paul E. Baker, Michael W. Fanger
Gamma Interferon Induces Monocytoid Differentiation In The Hl-60 Cell Line., Edward D. Ball, Paul M. Guyre, Li Shen, John M. Glynn, Charles R. Maliszewski, Paul E. Baker, Michael W. Fanger
Dartmouth Scholarship
We investigated the ability of purified, recombinant DNA-derived interferons (IFN) to induce phenotypic changes in cells of the HL-60 promyelocytic leukemia cell line. Changes in cell surface markers detected by monoclonal antibodies as well as morphologic, histochemical, and functional changes were monitored. We found that gamma-IFN, but not alpha- or beta-IFN, induced the expression of antigens characteristic of monocytes and granulocytes (AML-2-23, 63D3, and 61D3), as well as changes in morphology consistent with monocytoid differentiation. These included induction of alpha-naphthyl acetate esterase, increased cell size, and a decrease in azurophilic granules. The gamma-IFN dose dependency and time course of the …
Monoclonal Antibodies To Novel Myeloid Antigens Reveal Human Neutrophil Heterogeneity., Edward D. Ball, Robert F. Graziano, Li Shen, Michael W. Fanger
Monoclonal Antibodies To Novel Myeloid Antigens Reveal Human Neutrophil Heterogeneity., Edward D. Ball, Robert F. Graziano, Li Shen, Michael W. Fanger
Dartmouth Scholarship
Three cytotoxic murine monoclonal antibodies that recognize myeloid-specific antigens have been produced by immunization with normal human neutrophils or myeloblasts from a patient with acute myelomonocytic leukemia. Two of these, PMN 6 and PMN 29, are specific for neutrophils; the third monoclonal antibody, AML-2-23, is reactive with the majority of normal monocytes as well as a subpopulation of mature neutrophils. Although neutrophils from all individuals tested expressed these antigens, cytofluorographic analysis revealed that the percentage of cells bearing the PMN 6 and AML-2-23 antigens varied among individuals. Significant additional heterogeneity in the density of each antigen among antigen-bearing cells was …