Publikationsdatum:
2008-11-29
Beschreibung:
Most children with acute lymphoblastic leukemia (ALL) can be cured, but the prognosis is dismal for the minority of patients who relapse after treatment. To explore the genetic basis of relapse, we performed genome-wide DNA copy number analyses on matched diagnosis and relapse samples from 61 pediatric patients with ALL. The diagnosis and relapse samples typically showed different patterns of genomic copy number abnormalities (CNAs), with the CNAs acquired at relapse preferentially affecting genes implicated in cell cycle regulation and B cell development. Most relapse samples lacked some of the CNAs present at diagnosis, which suggests that the cells responsible for relapse are ancestral to the primary leukemia cells. Backtracking studies revealed that cells corresponding to the relapse clone were often present as minor subpopulations at diagnosis. These data suggest that genomic abnormalities contributing to ALL relapse are selected for during treatment, and they point to new targets for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746051/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746051/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mullighan, Charles G -- Phillips, Letha A -- Su, Xiaoping -- Ma, Jing -- Miller, Christopher B -- Shurtleff, Sheila A -- Downing, James R -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-30/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Nov 28;322(5906):1377-80. doi: 10.1126/science.1164266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19039135" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
B-Lymphocytes
;
Cell Cycle/genetics
;
Child
;
Cyclin-Dependent Kinase Inhibitor p15/genetics
;
Gene Deletion
;
*Gene Dosage
;
Genes, p16
;
*Genome, Human
;
Genomics
;
Humans
;
*Loss of Heterozygosity
;
Lymphopoiesis
;
Metabolic Networks and Pathways/genetics
;
*Mutation
;
Oligonucleotide Array Sequence Analysis
;
*Polymorphism, Single Nucleotide
;
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
;
Proto-Oncogene Proteins c-ets/genetics
;
Recurrence
;
Repressor Proteins/genetics
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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