# PROTEIN PATTERNS IN LEUKEMIC CELLS

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1993 · $213,985

## Abstract

This resubmission of a competing renewal application builds on
accomplishments made during prior support and progress made in the past
year, dealing with the characterization of two novel polypeptides in acute
lymphoblastic leukemia (ALL) that were detected using two-dimensional
polyacrylamide gel electrophoresis (2-D PAGE).  One polypeptide,
designated OP18 was identified as a highly conserved novel proliferation
regulated cytosolic phosphoprotein that appears to be involved in signal
transduction.  Unlike other proliferation regulated proteins we have
identified, OP18 is overexpressed at the protein and RNA levels in All
relative to nonleukemic proliferating lymphoid cells.  It is also
phosphorylated to a much lesser extent in acute leukemia cells.  In this
application, we propose to determine the role of OP18 in lymphoid
proliferation and to define more precisely the basis for differences in
OP18 phosphorylation observed between normal lymphoid cells and acute
leukemia, using well defined normal lymphoid cell populations obtained
from thymus and bone marrow.  Having completed genomic sequencing of Op18,
we also propose to study the regulation of Op18 gene expression by
identifying cis-acting elements using functional assays; by identifying
transcription factors involved in activation of the Op18 gene; and
determining which if any may be responsible for its overexpression in
leukemia.  Three polypeptides (L2,L3,L4) expressed in pre-B ALL, a
maturation defined subtype which accounts for most cases of ALL, were
identified as the phosphorylated and unphosphorylated forms of a heat
shock protein hsp27, not previously known to be constitutively expressed
in lymphoid cells outside of the heat shock response.  In pre-B ALL,
phosphorylation of hsp27 occurs to a variable extent among patients.  We
have ascertained through follow up that diminished phosphorylation of
hsp27 associated with poor prognosis.  We propose to study the mechanism
of phosphorylation of hsp27; to identify phosphorylation sites; and to
generate monoclonal antibodies to hsp27 phosphopeptides to allow studies
of hsp27 in bone marrow B lymphoid precursors and to more precisely
determine the extent of variability of hsp27 phosphorylation in pre-B ALL.
Clinical as well as laboratory features of ALL, which are a part of a
leukemia database we have developed, will be investigated to identify
which features may correlate with Op18 and hsp27 phosphorylation.  The
studies proposed are aimed at providing a better understanding of the
deregulated cell proliferation in ALL and of the biochemical basis of
heterogeneity observed between patients with pre-B ALL.

## Key facts

- **NIH application ID:** 3170148
- **Project number:** 5R01CA032146-08
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** SAMIR M HANASH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $213,985
- **Award type:** 5
- **Project period:** 1983-02-01 → 1997-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170148

## Citation

> US National Institutes of Health, RePORTER application 3170148, PROTEIN PATTERNS IN LEUKEMIC CELLS (5R01CA032146-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170148. Licensed CC0.

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