Adrian Woolfson

Analysis of human leukaemias and lymphomas using extensive immunophenotypes from an antibody microarray

A novel antibody microarray has been developed that provides an extensive immunophenotype of leukaemia cells. The assay is a solid phase cell‐capture technique in which 82 antigens are studied simultaneously. This paper presents the analysis of 733 patients with a variety of leukaemias and lymphomas from peripheral blood and bone marrow. Discriminant Function Analysis of the expression profiles from these 733 patients and 63 normal subjects were clustered and showed high levels of consistency with diagnoses obtained using conventional clinical and laboratory criteria. The overall levels of consensus for classification using the microarray compared with established criteria were 93·9% (495/527 patients) for peripheral blood and 97·6% (201/206 patients) for bone marrow aspirates, showing that the extensive phenotype alone was frequently able to classify the disease when the leukaemic clone was the dominant cell population present. Immunophenotypes for neoplastic cells were distinguishable from normal cells when the leukaemic cell count was at least 5 × 109 cells/l in peripheral blood, or 20% of cells obtained from bone marrow aspirates. This technique may be a useful adjunct to flow cytometry and other methods when an extensive phenotype of the leukaemia cell is desired for clinical trials, research and prognostic factor analysis.

Profiling CD antigens on leukaemias with an antibody microarray

Cluster of differentiation (CD) antigens are defined when a surface molecule found on some members of a standard panel of human cells reacts with at least one novel antibody, and there is good accompanying molecular data. Monoclonal antibodies to surface CD antigens on leukocytes have been used for flow cytometry, and more recently to construct microarrays that capture live cells. These DotScanTM microarrays enable the rapid and highly parallel characterization of repertoires of CD antigens whose expression patterns may be correlated with discrete leukaemia subtypes, or used to define biomarker ‘signatures’ for non‐hematological diseases. DotScanTM with fluorescence multiplexing enables profiling of CD antigens for minor subsets of cells, such as colorectal cancer cells and tumour‐infiltrating lymphocytes from a surgical sample.

Classification of AML using a monoclonal antibody microarray.

A cluster of differentiation (CD) antibody microarray called the DotScan microarray has been developed that enables an extensive immunophenotype to be obtained for a suspension of leukocytes in a single analysis. For a leukemia with a leukemia count of greater than 10 x 10(9)/L, the immunophenotype obtained is essentially that of the leukemic clone. The antibody microarray is printed as microscopic (10 nL) dots on a nitrocellulose film on a microscope slide. Cells are captured by the immobilized antibodies and a dot pattern is recorded with an optical array reader giving the immunophenotype of the leukemia. Procedures are being developed that should enable diagnosis of myeloid leukemias by comparison of the dot pattern obtained from an unknown blood sample with a library of consensus patterns for the common leukemias.

The Applicability of a Cluster of Differentiation Monoclonal Antibody Microarray to the Diagnosis of Human Disease

Recent advances in antibody microarray technology have facilitated the development of multiplexed diagnostic platforms. Highly parallel antigen expression data obtained from these arrays allow disease states to be characterized using protein patterns rather than individual protein markers. The development of an antibody microarray platform of general applicability requires careful consideration of the array content. The human cluster of differentiation (CD) antigens constitute a promising candidate set, being united by their common expression at the leukocyte cell surface and the fact that the majority perform critical functions in the human immune response. The diagnostic potential of a microarray, containing 82 cluster of differentiation monoclonal antibodies (DotScan microarrays) has been demonstrated for a variety of infectious and neoplastic disease states, including HIV, many acute and chronic leukemias, and colorectal cancer. It is likely that these microarrays will have more general utility that extends to other pathological categories, including autoimmune, metabolic, and degenerative diseases.

Winning the war

An insiders guide to the politics and personalities of Americas war on cancer In this engaging, provocative, and deeply personal book, Vincent DeVita and Elizabeth DeVita- Raeburn provide a compelling insiders guide into the personalities, organizations, and key protagonists that provided the backdrop and impetus for the unprecedented campaign known as the war on cancer. In addition to insightful (and sometimes unflattering) accounts of the major players in early cancer research and stories about DeVitas relentless attempts to identify appropriate therapies for friends, family and patients, The Death of Cancer presents a candid and disarming critique of the ways in which medicine, and specifically oncology, is regulated in the United States.

Inevitable or improbable

A biologist sheds light on the evolutionary likelihood of human existence In his compelling book Improbable Destinies, Jonathan Losos addresses the likelihood of human existence, recasting previous dialogues in the light of an experimental evolutionary agenda and, in so doing, arrives at a novel conclusion

Putting sleep myths to bed

From groggy teenagers to fatal insomnia, two tomes tackle the science of slumber Many of us have an ambivalent relationship with sleep. Although acknowledging its necessity, we begrudge these stolen hours of existence. Two new books-Henry Nicholls’s Sleepyhead and Alice Gregory’s Nodding Off- provide a fresh perspective on this poorly understood phenomenon. Rather than being an “imperfection of our nature,” as extolled by physician Wilson Phillip in 1833, sleep emerges as critical to healthy bodily, mental, and emotional function.

The messy biological basis of culture

Adrian Woolfson heralds Antonio Damasio’s bold argument that emotions define us. Adrian Woolfson heralds Antonio Damasio’s bold argument that emotions define us. SEM image of of strands of Streptomyces coelicoflavus.

Tinkering with evolution

A comprehensive tome explores the far-reaching implications of genome editing John Parringtons new book, Redesigning Life, is a comprehensive digest of the extraordinary scientific material relevant to the topic of gene editing. Parrington presents himself as the trusted tour guide of the latest developments in this rapidly advancing area of investigation, lacing his accounts with a number of charming analogies and anecdotes.

Crash and burn

Even ‘artificial organisms’ such as commercial companies find immortality out of reach.Stock answersWhy do most companies fail? A comparison of diverse complex systems, including corporations, species and government policies, seeks to establish whether failure can be explained by a general theory.