Alternative Telomere Lengthening

Thomas Mahoney excelife at earthlink.net
Thu Sep 16 23:29:43 EST 1999

My apologies,

I neglected to include the cite for the attached abstract.  It is; (Cancer 
Res 1999 Sep 1;59(17):4175-9)

Sorry for the oversight. 

Tom Mahoney

In article <7rrt9s$eke$1 at oak.prod.itd.earthlink.net>, excelife at earthlink.net 
>Most of the current research on immortalized cells have dealt with the 
>effects of the enzyme telomerase.  But some immortalized cell lines do not 
>show telomerase activity at all and are yet able to maintain telomeric 
>The following abstract describes how APBs, (see definition below), may be 
>factor that functions to maintain telomeric length in these cells.
>Studies to determine if APBs can maintain telomeric length in normal cells 
>and retain their normal phenotypical expression are currently under way.
>The implications being, that this would provide an additional method of 
>intervening in the aging of replicating cells, beyond those already known.
>Since some cells, such as T-cells, normally have telomerase activity, this 
>enzyme appears to be regulated by cellular mechanisms and the addition of 
>h-TERT alone may not have the desired effect of extending the cells lines 
>viable life span.  This alternative telomere maintenance system, (APBs), may 
>avoid the problem of cellular regulation of telomere maintenance systems.
>Telomerase-negative immortalized human cells contain a novel type of 
>promyelocytic leukemia (PML) body.
>Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR
>Children's Medical Research Institute, Westmead, Sydney, New South Wales, 
>Telomerase-negative immortalized human cells maintain their telomeres by a 
>mechanism known as alternative lengthening of telomeres (ALT). We report 
>that ALT cells contain a novel promyelocytic leukemia (PML) body 
>(ALT-associated PML body, APB). APBs are large donut-shaped nuclear 
>structures containing PML protein, telomeric DNA, and the telomere binding
>proteins human telomere repeat binding factors 1 and 2. Immunostaining 
>that APBs also contain replication factor A, RAD51, and RAD52, proteins 
>involved in DNA synthesis and recombination. During immortalization, APBs 
>appeared at exactly the same time as activation of ALT. APBs were found in 
>ALT tumors and cell lines but not in mortal cell strains or in 
>telomerase-positive cell lines or tumors.
>Thomas Mahoney, Pres.
>Lifeline Laboratories, Inc.

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