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2. Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies

Author

Seo, Sachiko, Renaud, Christian, Kuypers, Jane M., Chiu, Charles Y., Huang, Meei-Li, Samayoa, Erik, Xie, Hu, Yu, Guixia, Fisher, Cynthia E., Gooley, Ted A., Miller, Steven, Hackman, Robert C., Myerson, David, Sedlak, Ruth H., Kim, Yae-Jean, Fukuda, Takahiro, Fredricks, David N., Madtes, David K., Jerome, Keith R., and Boeckh, Michael

Published
2015
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4. Evaluation of Published Single-Nucleotide Polymorphisms (SNPs) Associated with Cytomegalovirus Infection and Disease after Hematopoietic Cell Transplantation in a Large Caucasian Cohort

Author

Seo, Sachiko, primary, Fan, Wenhong, additional, Hansen, John A., additional, Storer, Barry E., additional, Pergam, Steven A., additional, Green, Margaret L., additional, Ozkok, Sezen, additional, Goyal, Sonia, additional, Fisher, Cynthia, additional, Hingorani, Sangeeta, additional, Warren, Edus H., additional, Martin, Paul J., additional, Zhao, Lue Ping, additional, and Boeckh, Michael, additional

Published
2014
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5. Loss-of-function Additional sex combs like 1mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia

Author

Fisher, Cynthia L., Pineault, Nicolas, Brookes, Christy, Helgason, Cheryl D., Ohta, Hideaki, Bodner, Caroline, Hess, Jay L., Humphries, R. Keith, and Brock, Hugh W.

Abstract

The Additional sex combs like 1 (Asxl1)gene is 1 of 3 mammalian homologs of the Additional sex combs (Asx)gene of Drosophila. Asxis unusual because it is required to maintain both activation and silencing of Hoxgenes in flies and mice. Asxl proteins are characterized by an amino terminal homology domain, by interaction domains for nuclear receptors, and by a C-terminal plant homeodomain protein-protein interaction domain. A recent study of patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) revealed a high incidence of truncation mutations that would delete the PHD domain of ASXL1. Here, we show that Asxl1is expressed in all hematopoietic cell fractions analyzed. Asxl1knockout mice exhibit defects in frequency of differentiation of lymphoid and myeloid progenitors, but not in multipotent progenitors. We do not detect effects on hematopoietic stem cells, or in peripheral blood. Notably, we do not detect severe myelodysplastic phenotypes or leukemia in this loss-of-function model. We conclude that Asxl1 is needed for normal hematopoiesis. The mild phenotypes observed may be because other Asxlgenes have redundant function with Asxl1, or alternatively, MDS or oncogenic phenotypes may result from gain-of-function Asxlmutations caused by genomic amplification, gene fusion, or truncation of Asxl1.

Published
2010
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6. Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies.

Author

Sachiko Seo, Renaud, Christian, Kuypers, Jane M., Chiu, Charles Y., Meei-Li Huang, Samayoa, Erik, Hu Xie, Guixia Yu, Fisher, Cynthia E., Gooley, Ted A., Miller, Steven, Hackman, Robert C., Myerson, David, Sedlak, Ruth H., Yae-Jean Kim, Takahiro Fukuda, Fredricks, David N., Madtes, David K., Jerome, Keith R., and Boeckh, Michael

Subjects
*PNEUMONIA, *HEMATOPOIETIC stem cell transplantation, *BRONCHOALVEOLAR lavage, *POLYMERASE chain reaction, *GALACTOMANNANS, *ASPERGILLUS, *RHINOVIRUSES, *CYTOMEGALOVIRUSES
Abstract

Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N=20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV) and Aspergillus (N=8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = 0.03). Mortality in patients with only pathogens of 'uncertain' significance in lung was similar to that in patients with pathogens of 'established' significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia. [ABSTRACT FROM AUTHOR]

Published
2015
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