The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951.
OBJECTIVE
Deletion and methylation of the 9p21 chromosomal region are frequent in childhood acute lymphoblastic leukemia (ALL) but the prognostic significance is controversial. They inactivate CDKN2A, a gene encoding both p16INKa and p14ARF and, in some cases, contiguous genes that may influence chemosensitivity, such as CDKN2B encoding p15INKb or MTAP encoding methylthioadenosine phosphorylase.


METHODS
CDKN2A inactivation by deletion or methylation was studied using gene dosage and methyl-specific polymerase chain reaction.


RESULTS
Bi-allelic and mono-allelic inactivation were found in, respectively, 38 (17%) and 31 (14%) of 227 children with B-lineage ALL enrolled in EORTC trials. Although CDKN2A inactivation was more often associated with poor prognostic features in B-lineage ALL, it failed to influence the outcome of the patients significantly. Bi-allelic CDKN2B and MTAP co-inactivation were found in 36 (16%) and 24 (11%) of patients, respectively, and did not influence the 6-year event-free survival rate either, even when the analysis was restricted to CDKN2A inactivated ALL.


CONCLUSIONS
In this study of 227 cases of childhood B-lineage ALL, inactivation of CDKN2A, CDKN2B and MTAP did not influences the patients' outcome.
Mirebeau
Delphine
D
AP-HP, Paris, France.
Acquaviva
Cécile
C
Suciu
Stefan
S
Bertin
Raphaëlle
R
Dastugue
Nicole
N
Robert
Alain
A
Boutard
Patrick
P
Méchinaud
Francoise
F
Plouvier
Emmanuel
E
Otten
Jacques
J
Vilmer
Etienne
E
Cavé
Hélène
H
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D007223:Infant; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins