# CELLULAR TARGETS OF LEUKEMIC TRANSFORMATION

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1987 · $161,297

## Abstract

One of the major unanswered questions in the study of leukemogenesis
concerns the identity of the normal lymphohemopoietic precursor cells that
are transformed by various murine leukemia viruses.  In this proposal, we
plan to define the cellular origins of the thymus-dependent leukemias that
are induced in rats by the rat-adapted Gross leukemia virus (RAGV).  Our
working hypothesis, based on previous studies of RAGV-induced leukemias, is
that the leukemogenic targets of the RAGV are terminal deoxynucleotidyl
transferase-positive (TdT+) prothymocytes or their immediate precursors
(pre-TdT+ cells).

We will use two approaches to test this hypothesis.  In the first, we will
assess the ability of the RAGV to induce leukemic transformation in vivo in
purified populations of lymphohemopoietic stem and progenitor cells
isolated from rat bone marrow on the fluorescence-activated cell sorter
(FACS).  In the second, we will study the ability of TdT+ and pre-TdT+ bone
marrow cells, generated in a selective culture system, to be transformed in
vitro by the RAGV.  The leukemogenic potential of the virally transformed
cells from both systems will be determined by adoptive transfer assays,
using the RT-7 alloantigenic pan-T cell marker to determine the origin of
the leukemic T cells that arise in histocompatible LEW/NBR strain
chimeras.  The cellular targets of both the in vivo and in vitro
transformation experiments will be characterized and compared with each
other and with their preleukemic and leukemic descendants.  The efficiency
of leukemic transformation and viral infection within a defined target cell
population will be determined, using quantitative in vitro leukemic
colony-forming unit and focus-forming unit assays, respectively.  The time
course of appearance and the relative numbers of preleukemic and leukemic
cells will be traced, as will any progression in their differentiation and
leukemogenic potential.  The possible role of thymus epithelial cells in
enhancing the leukemogenic process and influencing the phenotype of the
leukemic cells will also be investigated.

The results of these studies should permit the leukemogenic process
initiated by the RAGV to be traced from the level of the normal precursor
cell to the preleukemic cell to the overtly leukemic cell.  Moreover, the
results will serve as a reference for comparative studies of the
leukemogenic targets of other MULVs; and may provide important insights
into the probable cellular origins of similar TdT+ lymphoblastic leukemias
and lymphomas that occur in human patients.

## Key facts

- **NIH application ID:** 3177017
- **Project number:** 5R01CA038762-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** IRVING GOLDSCHNEIDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $161,297
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177017

## Citation

> US National Institutes of Health, RePORTER application 3177017, CELLULAR TARGETS OF LEUKEMIC TRANSFORMATION (5R01CA038762-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177017. Licensed CC0.

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