# C-MYC REARRANGEMENTS IN HUMAN HEMATOPOIETIC NEOPLASIAS

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1993 · $306,249

## Abstract

The general objective of this research proposal is to elucidate the role
of chromosomal translocations involving the c-myc gene in the
pathogenesis of B-cell neoplasia.  In particular, the following lines of
investigation will be pursued: 1) Mechanism of c-myc oncogene
activation.  Chromosomal translocations are consistently associated with
removal or mutation of a specific 400 bp. 5' region of the c-myc gene.
The functional consequences of these mutations on c-myc gene regulation
will be investigated by studying: i) whether differently 5' mutated c-
myc alleles are abnormally regulated at the level of block of transcript
elongation, RNA stability or translation in transfected cells; and ii)
whether the 5' mutated region is involved in binding to regulatory (RNA-
or DNA-binding) proteins and the binding is affected by the mutations.;
2) Mechanism of c-myc gene autoregulation and its inactivation in tumor
cells.  c-myc gene expression is regulated by a negative autoregulatory
mechanism and this mechanism is blocked in tumor cells carrying either
normal or mutated c-myc genes.  We plan to further characterize this
mechanism and the cause of its inactivation by; i) identifying the c-myc
regulatory domains which are the targets for autoregulation of
transcription; and ii) determining whether the loss of c-myc
autoregulation is a dominant or recessive trait in tumor cells and
whether it is controlled by a specific chromosome; 3) Identification of
genes regulated by c-myc.  We will attempt to identify the genes which
are directly regulated by the heterodimeric myc/max transcriptional
complex by isolating myc/max-binding sequences (300-400 bp.) from total
genomic DNA by the "genomic PCR" purification method: 4) Relationship
between c-myc activation and p53 inactivation in BL.  Loss/inactivation
of the p53 tumor suppressor gene is specifically and consistently
associated with those B cell malignancies which carry activated c-myc
oncogenes and preliminary observations suggest that c-myc expression may
regulate p53.  Based on these observations we will: i) establish whether
and by which mechanism c-myc regulates p53 gene expression by studying
p53 expression in cell stably transfected with constitutive or inducible
c-myc vectors; and ii) determine the effects of p53 inactivation and the
combined effects of p53 inactivation and c-myc activation on the
phenotype (differentiation, clonogenicity, tumorigenicity, c-myc
autoregulation) of human B lymphoblastoid cells.  These studies should
extend our knowledge on the role of c-myc oncogene activation in
neoplasia by providing direct information on the nature of both the
genetic elements which regulate and are regulated by the c-myc gene.

## Key facts

- **NIH application ID:** 3174933
- **Project number:** 5R01CA037165-10
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** Riccardo Dalla-Favera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $306,249
- **Award type:** 5
- **Project period:** 1984-03-01 → 1997-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174933

## Citation

> US National Institutes of Health, RePORTER application 3174933, C-MYC REARRANGEMENTS IN HUMAN HEMATOPOIETIC NEOPLASIAS (5R01CA037165-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174933. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*