Biosynthesis of murine terminal deoxynucleotidyltransferase.

Silverstone, Allen E.; Sun, Leslie; Witte, Owen N.; Baltimore, David

doi:10.1016/s0021-9258(19)86249-x

Cited by 39 publications

(1 citation statement)

References 36 publications

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“…Murine TdT is known to have a molecular weight of 60,000 (52). As an independent means of identifying and quantitating the TdT activity in BALB-and Harvey-MSV transformants, we performed radioimmunoprecipitation analysis.…”

Section: Phenotype Of Balb-and Harvey-msv Hematopoietic Transformants To Define the Phenotype Of Balb-and Harvey-msv-transformed Hematopomentioning

confidence: 99%

BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.

Pierce¹,

Aaronson²

1982

The Journal of Experimental Medicine

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BALB- and Harvey-murine sarcoma viruses (MSV) comprise a family of retroviruses whose mouse- and rat-derived onc genes are closely related. These viruses induce sarcomas and erythroleukemias in susceptible animals. An in vitro colony assay that detects transformation of lymphoid cells by Abelson-murine leukemia virus was used to demonstrate that BALB- and Harvey-MSV transform a novel hematopoietic cell both in culture and in vivo. Bone marrow colony formation was sarcoma virus dependent, followed single-hit kinetics, and required the presence of mercaptoethanol in the agar medium. BALB- and Harvey-MSV-induced colonies could be established in culture as continuous cell lines that demonstrated unrestricted self-renewal capacity and leukemogenicity in vivo. The cells had a blast cell morphology and lacked detectable markers of mature cells within the myeloid or erythroid series. They also lacked detectable immunoglobulin mu chain or Thy-1 antigen, markers normally associated with committed cells of the B and T lymphoid lineages, respectively. However, the transformants contained very high levels of terminal deoxynucleotidyl transferase (TdT), an enzyme believed to be specific to early stages within the lymphoid differentiation pathway. This phenotype distinguishes these BALB- and Harvey-MSV transformants from any previously reported hematopoietic targets of transforming retroviruses, including the pre-B lymphoid cell transformed by Abelson-MuLV under identical assay conditions. These newly identified lymphoid progenitor cell transformants may provide an important means of studying early stages of lymphoid ontogeny and the possible role of TdT in lymphoid development.

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Section: Phenotype Of Balb-and Harvey-msv Hematopoietic Transformants To Define the Phenotype Of Balb-and Harvey-msv-transformed Hematopomentioning

confidence: 99%

BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.

Pierce¹,

Aaronson²

1982

The Journal of Experimental Medicine

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Measurement of terminal deoxynucleotidyl transferase mrna in clinical samples: A new parameter in analysis of leukemia cells

et al. 1987

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A 1750 base pair cDNA to human terminal deoxynucleotidyl transferase (TdT) has been cloned. This cDNA detects a dominant 2200 base pair messenger RNA species in normal and leukemic cells synthesizing the enzyme. A quantitative dot blot assay was utilized to survey a number of clinical samples from patients with TdT positive and negative leukemias as well as cells from normal volunteers. A linear relationship was detected between the amount of TdT mRNA and the amount of enzyme activity in bone marrow cells. The assay is sensitive enough to detect normal TdT levels in bone marrow, and distinguish these levels from the lack of such mRNA in peripheral blood and bone marrow of patients with myeloid leukemia. Elevated levels of mRNA were found in two cases of patients in clinical remission. The prognostic significance of these observations must await further study.

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Phorbol ester regulation of terminal deoxynucleotidyl transferase, proliferation, and TcR α in a pre‐T cell line

Béland

Yuille

Hugunin

et al. 1990

Journal Cellular Physiology

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Terminal deoxynucleotidyl transferase (TdT) is a template-independent DNA polymerase that is transiently expressed during the normal development of T and B lymphocytes. Phorbol 12-myristate 13-acetate (PMA) has been reported to induce maturation-like changes, including the loss of TdT, in many leukemic cell lines. We investigated the mechanism of TdT repression by PMA in an early thymocyte-like cell line, RPMI 8402. At a concentration of 8 nM, PMA caused both repression of TdT synthesis and arrest of proliferation. At greater concentrations of PMA, these same changes initially occurred, but then cell proliferation resumed, and TdT was reexpressed. At both 8 and 160 nM PMA, TdT biosynthesis and TdT mRNA became undetectable within 8 hours, while cell proliferation and DNA synthesis were not significantly reduced until 16 hours. Growth arrest induced by serum starvation did not result in a similar reduction of TdT RNA even after 48 hours. With 160 nM PMA, TdT mRNA could be detected again by 24 hours, and proliferation resumed. Transcription run-off assays indicated that TdT RNA synthesis ceased within 1 hour after exposure to both 8 and 160 nM PMA. T cell receptor alpha (TcR alpha) RNA was induced when TdT RNA was repressed. TcR beta RNA levels were unchanged, and TcR gamma RNA was up-regulated. TdT gene repression and modulation of cell proliferation as well as induction of TcR gene expression are normal events during intrathymic T cell maturation. This cell model provides a system for analyzing the molecular regulation of these significant developmental events.

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Biosynthesis of murine terminal deoxynucleotidyltransferase.

Cited by 39 publications

References 36 publications

BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.

BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.

Measurement of terminal deoxynucleotidyl transferase mrna in clinical samples: A new parameter in analysis of leukemia cells

Phorbol ester regulation of terminal deoxynucleotidyl transferase, proliferation, and TcR α in a pre‐T cell line

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