# A SPECIFIC ABNORMALITY IN CHRONIC LEUKEMIC LYMPHOCYTES

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1993 · $194,678

## Abstract

We have established that the L-system of amino acid transport is
invariably, and markedly impaired in the lymphocytes from patients with
B-cell chronic lymphocytic leukemia (CLL).  This highly specific difference
between CLL B-cells and normal B-cells will be exploited in an effort to
isolate and characterize the protein or proteins responsible for l-system
transport.  The membrane proteins from normal and CLL B-lymphocytes will be
separated using two dimensional gel electrophoresis.  Two methods will be
used to identify the L-system transport protein or proteins on two
dimensional gels.  Monoclonal antibodies that react specifically with the
L-system will be generated by making mice tolerant to CLL B-lymphocytes
which are deficient in the L-system and subsequently immunizing the mice
with normal B-lymphocytes which have an intact L-system.  The monoclonal
antibodies will be screened for reactivity to normal but not CLL B-cells.
Monoclonal antibodies binding to normal B but not CLL B-cells will be
screened for functional inhibition of the L-system.  Such antibodies can be
used to extend the sensitivity of two dimensional gel electrophoresis for
localization of the L-system transport protein.  In addition, photoreactive
radiolabelled amino acids which can be bound specifically to the L-system
site will be used to identify the transport protein on two dimensional
gels.  As an extension of previous investigations we will determine whether
the L-system transport in the T-lymphocyte population in CLL-B-cell
leukemia accounts for the 10% residual transport that is measured.  We will
separate the T-lymphocyte population from B-cell CLL blood using a
sepharose anti-immunoglobulin affinity column, and the measurements of
L-system transport will be correlated with the cytogenetics of the B and
T-cell populations.  Further, CLL B-cells will be treated with mitogenic
(cytochalasin B, staph protein A) and maturational (phorbol esters) agents
to determine the effect of 1) new DNA synthesis or 2) expression of the
plasma cell phenotype on the ability to acquire a heightened capacity of
L-system transport.  These studies will assess whether the impaired
L-system is related to a diminished proliferative capacity or arrested
maturation.

## Key facts

- **NIH application ID:** 3172463
- **Project number:** 5R01CA034691-10
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** GEORGE B SEGEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $194,678
- **Award type:** 5
- **Project period:** 1983-06-01 → 1995-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172463

## Citation

> US National Institutes of Health, RePORTER application 3172463, A SPECIFIC ABNORMALITY IN CHRONIC LEUKEMIC LYMPHOCYTES (5R01CA034691-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172463. Licensed CC0.

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