News Release

New insights into the genetic basis of resistance to chemotherapy in children with acute leukemia

Peer-Reviewed Publication

PLOS

In a new study published in PLoS Medicine, William Evans of St Jude Children’s Research Hospital, Memphis, and colleagues provide new insight into resistance to the widely-used cancer drug methotrexate (MTX) in patients with acute lymphoblastic leukaemia (ALL), the most common cancer in children.

ALL accounts for a quarter of all new childhood cancer cases every year in the United States. Children with ALL cannot fight even simple infections because genetic changes in immature lymphocytes – the white blood cells essential to the immune system – result in these cells dividing uncontrollably and failing to mature. The proliferation of these abnormal cells reduces the ability of the bone marrow to produce healthy blood cells. Children with ALL therefore are at increased risk of infection, and bruise and bleed easily, because they do not have enough white blood cells, red blood cells and platelets important for the clotting process.

Through chemotherapy treatment – a combination of drugs that kill the fast-dividing cells – more than 80% of children with ALL live for at least five years after diagnosis and are presumed cured. However, drug resistance, including resistance to MTX, is the biggest barrier to curing the remaining 20% of children. Why this resistance occurs is not well understood. The researchers in this study measured the effectiveness of MTX treatment in patients recently diagnosed with ALL. By taking samples of bone marrow and blood from patients before they were treated and by using microarray analysis to investigate gene expression in these leukemia cell samples, they found an association between the expression of 50 genes and the effectiveness of MTX in destroying the leukaemia cells. Patients who responded best to the drug (and who had the gene expression profile that indicated a good response) were more likely to be alive after five years than those with a worse response to MTX (and the genetic profile that indicated this poor response).

The findings suggest that genomic profiling could help predict response to this drug and the long-term survival of patients with ALL. They also suggest that new strategies to improve response to MTX are possible. Down-regulation of the expression of genes that are expressed more highly in those who don’t respond well to treatment is a plausible strategy to enhance survival rates. It also may be possible to increase the expression of those genes associated with a good response to improve the outlook of at least some of the children with ALL who fail to respond to current chemotherapy protocols.

Citation: Sorich MJ, Pottier N, Pei D, Yang W, Kager L, et al. (2008) In vivoresponse to methotrexate forecastsoutcome of acute lymphoblasticleukemia and has a distinct geneexpression profile. PLoS Med 5(4): e83.

IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050083

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-evans.pdf

CONTACT:

Carrie Strehlau
St. Jude Children's Research Hospital
Public Relations
332 N. Lauderdale St., Mail Stop 761
Memphis, TN 38105
United States of America
+1 901 495-2295
+1 901 495-3578 #2500
Carrie.Strehlau@stjude.org

William E. Evans
St. Jude Children's Research Hospital
Hematological Malignancies Program
332 N Lauderdale Street MS 272
Memphis, TN 38105
United States of America
+1 901-495-3301
william.evans@stjude.org


Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma

Kimberly Kelly of Harvard Medical School and colleagues describe the discovery of plectin-1 as a novel biomarker for pancreatic ductal adenocarcinoma and the subsequent development of a specific imaging probe using this marker.

Citation: Kelly KA, Bardeesy N, Anbazhagan R, Gurumurthy S, Berger J, et al. (2008) Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.

PLoS Med 5(4): e85.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE

VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050085

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-kelly.pdf

CONTACTS:
Kimberly Kelly
Harvard Medical School,
Center for Molecular Imaging Research
Charlestown, MA 01803
United States of America
+1 617-726-5788
+1 617 726-5708 (fax)
kkelly9@partners.org

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