Etiology and Pathogenesis of Mouse Leukemia

Miller, J. F. A. P.

doi:10.1016/s0065-230x(08)60623-5

Cited by 50 publications

(10 citation statements)

References 193 publications

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“…Finally, our evidence for the presence of Id + pre-B cells in these patients strongly suggests that the clonal oncogenic event that ultimately results in myeloma occurs within the bone marrow at the very earliest stage in B-cell development, and is not the consequence of antigen stimulation. This is in keeping with observations in mice indicating that T-cell malignancies invariably begin within the thymus (45) and in chickens that a B-cell malignancy originates within the bursal inductive microenvironment (46). Evidence from studies of malignancies of a variety of cell types suggests that the target cells for the oncogenic event are immature cells within the microenvironments in which they are normally induced to undergo specialized differentiation (47).…”

Section: Discussionsupporting

confidence: 91%

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

Kubagawa¹,

Vogler²,

Capra³

et al. 1979

The Journal of Experimental Medicine

230

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IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.

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Section: Discussionsupporting

confidence: 91%

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

Kubagawa¹,

Vogler²,

Capra³

et al. 1979

The Journal of Experimental Medicine

230

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“…It is well known that small lymphocytes are the cells responsible for defending the organism against foreign antigens circulating in the blood [14], and it seems reasonable to postulate that thymosin has a direct effect on the cells that are involved in immune reactions. The mechanism of thymosin's action may be explained either by stimulating lymphopoiesis (Metcalf proved that the thymus produces a cell-stimulating factor [15]), or by the induction of immune cell competence.…”

Section: The Effect Of the Thymic Hormone On Thymocyte Competencementioning

confidence: 99%

The Thymus: A Forgotten, But Very Important Organ

Zdrojewicz

Pachura²,

Pachura³

2015

Adv Clin Exp Med

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“…In 1958, Francis Albert Pierre Miller, after his medical degree and an internship at the Royal Prince Alfred Hospital in Sydney, received a research fellowship that enabled him to read for his PhD at the Chester Research Institute, an Institute of Cancer Research, in South Kensington, London, where Dr R. J. C. Harris suggested that he should investigate the pathogenesis of lymphocytic leukaemia in mice. This form, whether spontaneous or induced by irradiation or chemical agents, was known to involve the thymus, and adult thymectomy had prevented its development [6].…”

Section: The Thymus In Mouse Leukaemiamentioning

confidence: 99%

Miller’s seminal studies on the role of thymus in immunity

Ribatti

Crivellato

Vacca

2006

Clinical and Experimental Immunology

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SummaryThe thymus is one of the two primary lymphoid organs. It is responsible for the provision of T lymphocytes to the entire body, and provides a unique microenvironment in which T cell precursors (thymocytes) undergo development, differentiation and clonal expansion. This review article summarizes the seminal work of the Australian scientist Francis Albert Pierre Miller concerning the description for the first time of the crucial role of the thymus for normal development of the immune system.

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Etiology and Pathogenesis of Mouse Leukemia

Cited by 50 publications

References 193 publications

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

The Thymus: A Forgotten, But Very Important Organ

Miller’s seminal studies on the role of thymus in immunity

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