Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial.
Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.
Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
Hannah M
HM
Ensor
Claire
C
Schwab
Lisa J
LJ
Russell
Sue M
SM
Richards
Heather
H
Morrison
Dino
D
Masic
Lisa
L
Jones
Sally E
SE
Kinsey
Ajay J
AJ
Vora
Christopher D
CD
Mitchell
Christine J
CJ
Harrison
Anthony V
AV
Moorman
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018121:Receptors, Cytokine / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics; D014178:Translocation, Genetic
C498762:CRLF2 protein, human; D018121:Receptors, Cytokine; D018048:Receptors, Purinergic P2