# VIRAL MALIGNANT LYMPHOMAGENESIS IN X-IRRADIATED MICE

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1987 · $206,206

## Abstract

Tumor progression is a critical step in lymphomagenesis.  It is a
little-understood process.  In murine lymphomagenesis we have found three
distinct phases of T cell neoplasms:  T cell neoplasms of phase I, which we
shall call T cell lymphoblastoma (TCLB), consist of cells that are normal
diploid, growth factor dependent, do not clone in soft agar, and do not
grow under the skin in vivo.  TCLB cells are autostimulating, genetically
stable tumor cells.  In contrast T cell neoplasms of phase III, which we
shall call T cell lymphomas (TCL), contain cells capable of autonomous
growth which can be cloned quantitatively in soft agar and which are
tumorigenic when inoculated under the skin of mice.  Phase III TCL cells
are often trisomic for chromosome 15 and highly stable genetically; they
originate in the thymus.  T cell neoplasms of phase II have properties
intermediate between neoplasms of phase I and phase III.  The essence of
progression of phase I cells to phase III consists of the gradual
development of growth factor independence.  Phase I cells progress to phase
II and possibly to phase III cells, a process accompanied by increasing
autonomy of the cells.  We will study the mechanism of this progression.

TCLB- and TCL cells will be tested for the expression of cellular
oncogenes.  Poly (A+) RNA extracted from cultured neoplastic T cells of
phases I, II, and III, will be hybridized following separation on agorose
gels and "Northern blotting".  Nick-translated probes made to 14 different
cloned oncogenes, C-type viral long terminal repeats (LTR) and viral
envelope sequences will be used.  The level of expression as well as gene
rearrangements will be sought and correlated with chromosome abnormalities
that are present in the karyotypes of the neoplastic cells of phases II and
III.  Expression and/or rearrangement of genes associated with T cell
proliferation (e.g. interleukin-2) will also be studied, as will the
phenotypic differences among TCLB and TCL cells of the three phases.

Activation of transforming genes in karyotypically different TCL clones
will be studied by means of DNA-mediated gene transfer.  NIH 3T3- and
lymphoid (TCLB) cells will be transfected with DNA isolated from TCL
clones.  Sensitivity to digestion with restriction enzymes of transforming
DNAs isolated from different TCL clones will be used to delineate the
transforming genes present in different TCL clones.

Polyclonal B cell lymphoblastomas (BCLB) have been induced in B6 mice by a
potent C-type virus complex.  The pathogenic virus will be sought and will
be molecularly cloned.  Viral genes active in the induction of BCLB will be
studied by constructing site-specific virus recombinants.

## Key facts

- **NIH application ID:** 3171918
- **Project number:** 5R01CA034151-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** Martin nmi Haas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $206,206
- **Award type:** 5
- **Project period:** 1982-05-01 → 1988-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171918

## Citation

> US National Institutes of Health, RePORTER application 3171918, VIRAL MALIGNANT LYMPHOMAGENESIS IN X-IRRADIATED MICE (5R01CA034151-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171918. Licensed CC0.

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