Document Detail


Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study.
MedLine Citation:
PMID:  22210879     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene expression profiling was performed on 97 cases of infant ALL from Children's Oncology Group Trial P9407. Statistical modeling of an outcome predictor revealed 3 genes highly predictive of event-free survival (EFS), beyond age and MLL status: FLT3, IRX2, and TACC2. Low FLT3 expression was found in a group of infants with excellent outcome (n = 11; 5-year EFS of 100%), whereas differential expression of IRX2 and TACC2 partitioned the remaining infants into 2 groups with significantly different survivals (5-year EFS of 16% vs 64%; P < .001). When infants with MLL-AFF1 were analyzed separately, a 7-gene classifier was developed that split them into 2 distinct groups with significantly different outcomes (5-year EFS of 20% vs 65%; P < .001). In this classifier, elevated expression of NEGR1 was associated with better EFS, whereas IRX2, EPS8, and TPD52 expression were correlated with worse outcome. This classifier also predicted EFS in an independent infant ALL cohort from the Interfant-99 trial. When evaluating expression profiles as a continuous variable relative to patient age, we further identified striking differences in profiles in infants less than or equal to 90 days of age and those more than 90 days of age. These age-related patterns suggest different mechanisms of leukemogenesis and may underlie the differential outcomes historically seen in these age groups.
Authors:
Huining Kang; Carla S Wilson; Richard C Harvey; I-Ming Chen; Maurice H Murphy; Susan R Atlas; Edward J Bedrick; Meenakshi Devidas; Andrew J Carroll; Blaine W Robinson; Ronald W Stam; Maria G Valsecchi; Rob Pieters; Nyla A Heerema; Joanne M Hilden; Carolyn A Felix; Gregory H Reaman; Bruce Camitta; Naomi Winick; William L Carroll; ZoAnn E Dreyer; Stephen P Hunger; Cheryl L Willman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-30
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-24     Completed Date:  2012-05-21     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1872-81     Citation Subset:  AIM; IM    
Affiliation:
University of New Mexico Cancer Center and Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carrier Proteins / genetics
Cluster Analysis
Cohort Studies
DNA-Binding Proteins / genetics
Female
Gene Expression Profiling*
Gene Expression Regulation, Leukemic*
Gene Regulatory Networks
Homeodomain Proteins / genetics
Humans
Infant
Kaplan-Meier Estimate
Male
Models, Genetic
Myeloid-Lymphoid Leukemia Protein / genetics
Nuclear Proteins / genetics
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Fusion / genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy,  genetics*
Prognosis
Transcription Factors / genetics
Treatment Outcome
Tumor Suppressor Proteins / genetics
fms-Like Tyrosine Kinase 3 / genetics
Grant Support
ID/Acronym/Agency:
P30 CA118100/CA/NCI NIH HHS; R01 CA080175/CA/NCI NIH HHS; U01 CA114762/CA/NCI NIH HHS; U10 CA098543/CA/NCI NIH HHS; U10 CA98413/CA/NCI NIH HHS; U24 CA114766/CA/NCI NIH HHS; UL1 TR000041/TR/NCATS NIH HHS; UL1 TR000064/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Homeodomain Proteins; 0/IRX2 protein, human; 0/Nuclear Proteins; 0/Oncogene Proteins, Fusion; 0/TACC2 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; 150826-18-9/AFF1 protein, human; EC 2.7.10.1/FLT3 protein, human; EC 2.7.10.1/fms-Like Tyrosine Kinase 3
Comments/Corrections

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