viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia.
2013; 31 (6): 545-552
Pediatric Acute Myeloid Leukemia as Classified Using 2008 WHO Criteria: A Single-Center Experience.
American journal of clinical pathology
2013; 139 (6): 818-825
New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map high-dimensional cytometry data onto two dimensions, yet conserve the high-dimensional structure of the data. viSNE plots individual cells in a visual similar to a scatter plot, while using all pairwise distances in high dimension to determine each cell's location in the plot. We integrated mass cytometry with viSNE to map healthy and cancerous bone marrow samples. Healthy bone marrow automatically maps into a consistent shape, whereas leukemia samples map into malformed shapes that are distinct from healthy bone marrow and from each other. We also use viSNE and mass cytometry to compare leukemia diagnosis and relapse samples, and to identify a rare leukemia population reminiscent of minimal residual disease. viSNE can be applied to any multi-dimensional single-cell technology.
View details for DOI 10.1038/nbt.2594
View details for PubMedID 23685480
Ikaros: master of hematopoiesis, agent of leukemia.
Therapeutic advances in hematology
2011; 2 (6): 359-368
The classification of acute myeloid leukemia (AML) has evolved to the most recent World Health Organization (WHO) schema, which integrates genetic, morphologic, and prognostic data into a single system. However, this system was devised using adult data and how this system applies to a pediatric cohort is unknown. Performing a retrospective chart review, we examined our single-center experience with AML in 115 children and classified their leukemia using the WHO 2008 schema. We examined patient samples for mutations of FLT3, NPM1, and CEBPA. Overall survival was calculated within categories. In our pediatric population, most cases of AML had recurrent genetic abnormalities of favorable prognosis. More than 10% of patients in our series were categorized as AML, with myelodysplasia-related changes, an entity not well-described in pediatric patients. In addition, a large proportion of patients were categorized with secondary, therapy-related AML. To our knowledge, this is the first application of the WHO 2008 classification to a pediatric cohort. In comparison to adult studies, AML in the pediatric population shows a distinct distribution within the WHO 2008 classification.
View details for DOI 10.1309/AJCP59WKRZVNHETN
View details for PubMedID 23690127
Speeding the Flow Toward Personalized Therapy in Childhood Acute Leukemia
PEDIATRIC BLOOD & CANCER
2009; 53 (4): 525-526
Why Are Young Infants Tested for Herpes Simplex Virus?
PEDIATRIC EMERGENCY CARE
2008; 24 (10): 673-678
Ikaros is the founding member of a family of zinc finger transcription factors whose function during early hematopoietic development is required for differentiation into the three major hematopoietic lineages. Ikaros deletions have been described in human malignancies, particularly precursor B-cell leukemia. Deletions of this transcription factor appear to mediate leukemogenesis, although the exact mechanism is unclear. This article reviews the structure and function of Ikaros proteins in chromatin remodeling and gene expression as well as the current knowledge of Ikaros deletions in human malignancies. A new proteomic platform, mass cytometry, is introduced which allows measurements of greater than 30 parameters at the single-cell level and should thus provide a greater level of detail to unravel the mechanistic consequences of Ikaros dysfunction in leukemia.
View details for DOI 10.1177/2040620711412419
View details for PubMedID 23556102
The polymerase chain reaction (PCR)-based test to detect herpes simplex virus (HSV) genome in cerebrospinal fluid (CSF) has become the test of choice for diagnosing this infection. The utility of this test in young infants undergoing sepsis evaluations is unknown.We sought to identify the factors that prompted physicians to include HSV PCR in their evaluation of young infants undergoing lumbar puncture. In addition, the impact of ordering this test on patient management was assessed.This case-control study included infants 0 to 60 days who were evaluated by lumbar puncture at the Alfred I. duPont Hospital for Children over a 5-year period. Case patients had CSF HSV PCR ordered as part of their evaluation and control patients did not.Eighty-eight case patients and 83 control patients were identified. The median patient age was 12 days and most patients (55%) were male. Both groups were similar in demographics. Herpes simplex virus infection was diagnosed by PCR in 3.4% of cases. The occurrence of a seizure (adjusted odds ratio [OR], 8.3; 95% confidence interval [CI], 1.7-41.0), the performance of CSF enteroviral PCR testing (adjusted OR, 4.7; 95% CI, 1.4-15.8), and the decision to obtain hepatic transaminases (adjusted OR, 5.6; 95% CI, 2.7-11.8) were associated with the decision to perform CSF HSV PCR testing. Use of health care resources associated with PCR testing was considerable.The occurrence of a seizure, the performance of CSF enteroviral PCR testing, and the decision to obtain hepatic transaminases were independently associated with the decision to perform CSF HSV PCR testing. Features traditionally associated with neonatal HSV infection, such as elevated numbers of CSF white blood cells or red blood cells, did not appear to influence the decision to perform CSF HSV PCR testing. The yield of testing in this population was low. Clinicians should weigh the benefits of early diagnosis in a few patients against the consequences of excessive testing in this population.
View details for Web of Science ID 000260157500006
View details for PubMedID 19242136