Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia

A Children's Oncology Group study

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 & 3 others ZoAnn E. Dreyer, Stephen P. Hunger, Cheryl L. Willman

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1872-1881
Number of pages10
JournalBlood
Volume119
Issue number8
DOIs
StatePublished - Feb 23 2012

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Oncology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transcriptome
Gene expression
Disease-Free Survival
Classifiers
Genes
Gene Expression Profiling
Age Groups
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kang, H., Wilson, C. S., Harvey, R. C., Chen, I. M., Murphy, M. H., Atlas, S. R., ... Willman, C. L. (2012). Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: A Children's Oncology Group study. Blood, 119(8), 1872-1881. https://doi.org/10.1182/blood-2011-10-382861

Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia : A Children's Oncology Group study. / Kang, Huining; Wilson, Carla S.; Harvey, Richard C.; Chen, I. Ming; Murphy, Maurice H.; Atlas, Susan R.; Bedrick, Edward J.; Devidas, Meenakshi; Carroll, Andrew J.; Robinson, Blaine W.; Stam, Ronald W.; Valsecchi, Maria G.; Pieters, Rob; Heerema, Nyla A.; Hilden, Joanne M.; Felix, Carolyn A.; Reaman, Gregory H.; Camitta, Bruce; Winick, Naomi; Carroll, William L.; Dreyer, ZoAnn E.; Hunger, Stephen P.; Willman, Cheryl L.

In: Blood, Vol. 119, No. 8, 23.02.2012, p. 1872-1881.

Research output: Contribution to journalArticle

Kang, H, Wilson, CS, Harvey, RC, Chen, IM, Murphy, MH, Atlas, SR, Bedrick, EJ, Devidas, M, Carroll, AJ, Robinson, BW, Stam, RW, Valsecchi, MG, Pieters, R, Heerema, NA, Hilden, JM, Felix, CA, Reaman, GH, Camitta, B, Winick, N, Carroll, WL, Dreyer, ZE, Hunger, SP & Willman, CL 2012, 'Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: A Children's Oncology Group study', Blood, vol. 119, no. 8, pp. 1872-1881. https://doi.org/10.1182/blood-2011-10-382861
Kang, Huining ; Wilson, Carla S. ; Harvey, Richard C. ; Chen, I. Ming ; Murphy, Maurice H. ; Atlas, Susan R. ; Bedrick, Edward J. ; Devidas, Meenakshi ; Carroll, Andrew J. ; Robinson, Blaine W. ; Stam, Ronald W. ; Valsecchi, Maria G. ; Pieters, Rob ; Heerema, Nyla A. ; Hilden, Joanne M. ; Felix, Carolyn A. ; Reaman, Gregory H. ; Camitta, Bruce ; Winick, Naomi ; Carroll, William L. ; Dreyer, ZoAnn E. ; Hunger, Stephen P. ; Willman, Cheryl L. / Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia : A Children's Oncology Group study. In: Blood. 2012 ; Vol. 119, No. 8. pp. 1872-1881.
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abstract = "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.",
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T1 - Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia

T2 - A Children's Oncology Group study

AU - Kang, Huining

AU - Wilson, Carla S.

AU - Harvey, Richard C.

AU - Chen, I. Ming

AU - Murphy, Maurice H.

AU - Atlas, Susan R.

AU - Bedrick, Edward J.

AU - Devidas, Meenakshi

AU - Carroll, Andrew J.

AU - Robinson, Blaine W.

AU - Stam, Ronald W.

AU - Valsecchi, Maria G.

AU - Pieters, Rob

AU - Heerema, Nyla A.

AU - Hilden, Joanne M.

AU - Felix, Carolyn A.

AU - Reaman, Gregory H.

AU - Camitta, Bruce

AU - Winick, Naomi

AU - Carroll, William L.

AU - Dreyer, ZoAnn E.

AU - Hunger, Stephen P.

AU - Willman, Cheryl L.

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N2 - 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.

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