TY - JOUR
T1 - Incidence and clinical significance of CDKN2/MTS1/P16(ink4a) and MTS2/P15(ink4b) gene deletions in childhood acute lymphoblastic leukemia
AU - Zhou, Muxiang
AU - Gu, Lubing
AU - Yeager, Andrew M.
AU - Findley, Harry W.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - 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 x 109 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.
AB - 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 x 109 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.
KW - p16/p15gene deletion
KW - pediatric acute lymphoblastic leukemia
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U2 - 10.3109/08880019709030900
DO - 10.3109/08880019709030900
M3 - Article
C2 - 9089742
AN - SCOPUS:0030941174
VL - 14
SP - 141
EP - 150
JO - Pediatric Hematology and Oncology
JF - Pediatric Hematology and Oncology
SN - 0888-0018
IS - 2
ER -