Incidence and clinical significance of CDKN2/MTS1/P16ink4A and MTS2/P15ink4B gene deletions in childhood acute lymphoblastic leukemia.
We have examined the incidence and clinical significance of deletions of two candidate tumor suppressor genes, CDKN2/MTS1/p16ink4A and MTS2/p15ink4B, in pediatric acute lymphoblastic leukemia (ALL). Gene deletion was evaluated in leukemic bone marrow (BM) cells obtained at diagnosis from 105 pediatric ALL patients: 83 with B-cell precursor (BCP-ALL) ALL and 22 with T-ALL. CDKN2/p16 deletion was seen in 23 of the 83 (28%) BCP-ALL and 15 of the 22 (68%) T-ALL cases. A virtually identical pattern of MTS2/p15 deletion was detected in these patients: p15 was deleted in 37 of 38 cases with p16 deletion, and p15 was not deleted in any p16-positive specimens. P16/p15 deletions were significantly related to poor prognosis factors including age under 1 year (P < 0.001), initial white cell counts greater than 50 x 10(9) per liter (P < .001), and T cell phenotype P < .005). Analysis of all 105 patients revealed that the 5-year disease-free survival rate was 68% for patients without p16/p15 deletions and 35% for those with p16/p15 deletions (P < .005). The association between gene deletion at initial diagnosis and unfavorable outcome suggests that loss of these genes is clinically significant and indicates a need for prospective studies of p16/p15 deletion in pediatric ALL patients.
Zhou
M
M
Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Gu
L
L
Yeager
A M
AM
Findley
H W
HW
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000503:physiopathology; D011379:Prognosis; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins