# MOLECULAR GENETICS OF LYMPHOID NEOPLASIA

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1993 · $25,272

## Abstract

The present application proposes to analyze the molecular structure of a
number of recurring chromosome abnormalities associated with lymphoid
and myeloid neoplasia that share a breakpoint at 11q23, to clone the
breakpoint junctions, to search for the genes associated with the
breakpoints, and to study their structure and expression. The underlying
hypothesis is that genes involved in the regulation of lymphoid and
myeloid cell proliferation and differentiation at either 11q23 or at the
associated breakpoints sites, are activated to oncogenes by the
chromosome rearrangements, and that this is an important step in
oncogenesis for lymphoid and myeloid neoplasia. It is also important to
determine which are the mechanisms by which these chromosome
rearrangements arise, to identify predisposing factors and to devise
prophylactic measures to reduce the risk of leukemia and lymphoma.

We have mapped the breakpoints of three different translocations:
t(9;11)(p22;q23) of monocytic leukemia, t(11;19)(q23;p13) of
myeloblastic or lymphoblastic leukemias, and t(4;11)(q21;q23) of
lymphoblastic leukemia with cell surface myeloid markers, to a region of
about 90 kb within band 11q23. Cloned DNA sequences from inside this
region will be used to screen Southern blots, prepared from leukemic
cells DNA, to detect rearrangements corresponding to the breakpoint
junctions; then, the DNA sequences across the junction will be cloned to
search for associated genes. The nucleotide sequence around the junction
will provide information about possible mechanisms of origin of the
rearrangement.

The genomic sequences likely to contain putative oncogenes will be
identified by looking for DNA sequences that cross hybridize to unique
sequences in other vertebrate species, that identify transcripts in a
northern blot, or that lie close to CpG islands. The genes identified
will be cloned as CDNAS, their proteins will be expressed in bacterial
vectors, and antibodies will be prepared to analyze their expression.
The oncogenic nature of these genes, and their effects on the phenotype
of hematopoietic cells will be tested by transfecting appropriate
constructs into lymphoid or myeloid cell in culture.

In order to immortalize these chromosome rearrangements, cell lines will
be established from the primary leukemia cells. These and previously
established cell lines will be used to study the expression of genes
found in association with the breakpoints.

A t(1;7)(p34;q34) involving the TCRB gene has been analyzed in the cell
line HSB2. The LCK gene coding for a T-cell specific tyrosine-protein-
kinase has been found involved at the 1p34 breakpoint. The analysis of
this abnormality will be continued, to determine the mechanism of
activation of LCK.

## Key facts

- **NIH application ID:** 3176956
- **Project number:** 5R01CA038725-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** MANUEL ORESTES DIAZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $25,272
- **Award type:** 5
- **Project period:** 1987-08-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176956

## Citation

> US National Institutes of Health, RePORTER application 3176956, MOLECULAR GENETICS OF LYMPHOID NEOPLASIA (5R01CA038725-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176956. Licensed CC0.

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