Incidence and Clinical Significance of CDKN2/MTS1/P16ink4AND MTS2/P15ink4BGene Deletions in Childhood Acute Lymphoblastic Leukemia

Abstract

We have examined the incidence and clinical significance of deletions of two candidate tumor suppressor genes, CDKN2/MTS1/p16^ink4A and MTS2/p15^ink4B, 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 × 10⁹per 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 p 16/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.