TY - JOUR
T1 - Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia
T2 - A Children's Oncology Group Study
AU - Chen, I. Ming
AU - Harvey, Richard C.
AU - Mullighan, Charles G.
AU - Gastier-Foster, Julie
AU - Wharton, Walker
AU - Kang, Huining
AU - Borowitz, Michael J.
AU - Camitta, Bruce M.
AU - Carroll, Andrew J.
AU - Devidas, Meenakshi
AU - Pullen, D. Jeanette
AU - Payne-Turner, Debbie
AU - Tasian, Sarah K.
AU - Reshmi, Shalini
AU - Cottrell, Catherine E.
AU - Reaman, Gregory H.
AU - Bowman, W. Paul
AU - Carroll, William L.
AU - Loh, Mignon L.
AU - Winick, Naomi J.
AU - Hunger, Stephen P.
AU - Willman, Cheryl L.
PY - 2012/4/12
Y1 - 2012/4/12
N2 - As controversy exists regarding the prognostic significance of genomic rearrangements of CRLF2 in pediatric B-precursor acute lymphoblastic leukemia (ALL) classified as standard/intermediate-risk (SR) or high-risk (HR), we assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomic lesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes frequently associated with high CRLF2 expression (IKZF1, JAK, IL7R), and minimal residual disease (MRD) in 1061 pediatric ALL patients (499 HR and 562 SR) on COG Trials P9905/P9906. Whereas very high CRLF2 expression was found in 17.5% of cases, only 51.4% of high CRLF2 expressors had CRLF2 genomic lesions. The mechanism underlying elevated CRLF2 expression in cases lacking known genomic lesions remains to be determined. All CRLF2 genomic lesions and virtually all JAK mutations were found in high CRLF2 expressors, whereas IKZF1 deletions/mutations were distributed across the full cohort. In multivariate analyses, NCI risk group, MRD, high CRLF2 expression, and IKZF1 lesions were associated with relapse-free survival. Within HRALL, only MRD and CRLF2 expression predicted a poorer relapse-free survival; no difference was seen between cases with or without CRLF2 genomic lesions. Thus, high CRLF2 expression is associated with a very poor outcome in high-risk, but not standard-risk, ALL. This study is registered at www.clinicaltrials.gov as NCT00005596 and NCT00005603.
AB - As controversy exists regarding the prognostic significance of genomic rearrangements of CRLF2 in pediatric B-precursor acute lymphoblastic leukemia (ALL) classified as standard/intermediate-risk (SR) or high-risk (HR), we assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomic lesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes frequently associated with high CRLF2 expression (IKZF1, JAK, IL7R), and minimal residual disease (MRD) in 1061 pediatric ALL patients (499 HR and 562 SR) on COG Trials P9905/P9906. Whereas very high CRLF2 expression was found in 17.5% of cases, only 51.4% of high CRLF2 expressors had CRLF2 genomic lesions. The mechanism underlying elevated CRLF2 expression in cases lacking known genomic lesions remains to be determined. All CRLF2 genomic lesions and virtually all JAK mutations were found in high CRLF2 expressors, whereas IKZF1 deletions/mutations were distributed across the full cohort. In multivariate analyses, NCI risk group, MRD, high CRLF2 expression, and IKZF1 lesions were associated with relapse-free survival. Within HRALL, only MRD and CRLF2 expression predicted a poorer relapse-free survival; no difference was seen between cases with or without CRLF2 genomic lesions. Thus, high CRLF2 expression is associated with a very poor outcome in high-risk, but not standard-risk, ALL. This study is registered at www.clinicaltrials.gov as NCT00005596 and NCT00005603.
UR - http://www.scopus.com/inward/record.url?scp=84859820034&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-11-394221
DO - 10.1182/blood-2011-11-394221
M3 - Article
C2 - 22368272
AN - SCOPUS:84859820034
SN - 0006-4971
VL - 119
SP - 3512
EP - 3522
JO - Blood
JF - Blood
IS - 15
ER -