==========================
                        JeffNEWS, January 10, 1995
                        ==========================


Leukemia Loses Another Battle to Jefferson Cancer Researchers
-------------------------------------------------------------

Researchers at Jefferson, in collaboration with Raggio-Italgene, SpA, of
Italy, have identified and characterized TCL-1 - a gene that can cause
several types of devastating leukemias and lymphomas. The work appeared
in studies published in Proceedings of the National Academy of Sciences
(PNAS) and Cancer Research  in December 1994. Stopping expression of
TCL-1 in humans would cure patients who have a variety of low-grade
leukemias and lymphomas, such as T-cell prolymphocytic leukemia, T-cell
chronic lymphocytic leukemia and adult T-cell leukemia.

There are two types of T-cell malignancies:  high-grade and low-grade.
Until now, no one has been able to identify a gene specific for
low-grade T-cell leukemia.

"Our analysis of TCL-1 indicates that it is one of a new family of genes
that is involved with the prolif-eration of T-cell and B-cell
malignancies. We hope that we will be able to develop a test to indicate
when this gene has been activated and to devise a way to shut off its
expression," said Carlo M. Croce, MD, professor and chairman of
department of microbiology and immunology, Jefferson Medical College,
and director of the Jefferson Cancer Institute and the Jefferson Cancer
Center.

In the first study, which appeared in the December 20 issue of PNAS, the
researchers mapped and cloned the TCL-1 gene on chromosome 14. This
chromosome was recognized as being frequently involved in chromosomal
translocations and inversions that cause human T-cell leukemias and
lymphomas.

"Using a variety of technologies, we were able to finally identify TCL-1
and prove that it was involved in low-grade and intermediate-grade
T-cell malignancies, including adult T-cell leukemia, which we
previously thought was caused by a virus," said Giandomenico Russo, MD,
head of the genetics program at Raggio-Italgene. Several of the
breakpoints involved in the translocations on chromosome 14 had been
previously characterized, but the TCL-gene had not been identified due
to the large region of DNA that was involved.

In the second study, which appeared in the December 15 issue of Cancer
Research, the researchers determined that TCL-1 is primarily expressed
in the lymphoid cells. They also pinpointed the gene's chromosomal
location by cloning numerous breakpoints on chromosome 14 and placing
the breakpoints on a map of the region. In the study, TCL-1 exhibited
remarkable similarities to the gene involved in rare chromosomal
translocations in T- cell proliferative disorders - MTCP-1. These
similarities indicate that both genes are members of the same gene
family, and that both control lymphoid cell proliferation and/or
survival and can cause T-cell malignancies.

Chromosomal translocations and inversions often occur in human T-cells
and B-cells as a consequence of mistakes during the normal process of
recombination of the genes for immunoglobulin and T-cell receptor
production. T-cells are lymphocytes that are primarily responsible for
cell-mediated immunity. They originate from lymphoid stem cells that
migrate from the bone marrow to the thymus. B-cells are lymphocytes that
are primarily responsible for the production of antibodies.

Dr. Croce has led a variety of research efforts against leukemia. Most
recently, a group of Jefferson researchers found that the genetic
mechanism for acute leukemia involves the partial duplication of the
ALL-1 gene - a gene found on chromosome 11 that is associated with
several common forms of acute leukemias.

It is hoped that research like this will be the deciding weapon in the
war against leukemia.

These Jefferson research projects were partially supported by the
National Institutes of Health and Raggio-Italgene, SpA.


------------------------------------------------------------------------------
Information provided by:  Editor, JeffNEWS
                          (215) 955-6204
------------------------------------------------------------------------------