A rogue chromosome - dubbed the Philadelphia chromosome - is responsible for a type of leukaemia known clinically as chronic myelogenous leukaemia, or CML, and for a subset of another type of leukaemia called acute lymphoblastic leukaemia, or ALL. This abnormal chromosome produces a version of a signalling protein that causes bone marrow cells to multiply uncontrollably. A paper in Nature identifies another mutant protein that contributes to this catastrophic process in ALL patients.
James Downing and colleagues examined the genetic material of 304 ALL patients and found that over 80% of those carrying the lesion associated with the Philadelphia chromosome also lacked a gene known as IKZF1. The protein encoded by this gene, called Ikaros, is a transcription factor, normally responsible for mediating DNA read-out via an RNA intermediate.
The authors conclude that genetic lesions resulting in the loss of Ikaros activity cause a crucial malfunctioning that can contribute to the development of ALL in people carrying the Philadelphia lesion.
James Downing (St Jude Children's Research Hospital, Memphis, USA)
Abstract available online.
(C) Nature press release.
Message posted by: Trevor M. D'Souza
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