J Cancer 2015; 6(11):1114-1120. doi:10.7150/jca.11959
CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients
1. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou Dadao North Street, 1838, Guangzhou 510515, China
2. Department of Management and Development, Nanfang Hospital, Southern Medical University, Guangzhou Dadao North Street, 1838, Guangzhou 510515, China
* Na Xu and Yuling Li contributed equally to this study and should be considered as co-first authors
Xu N, Li Yl, Zhou X, Cao R, Li H, Lu Qs, Li L, Lu Zy, Huang Jx, Sun J, Liu Qf, Du Qf, Liu Xl. CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients. J Cancer 2015; 6(11):1114-1120. doi:10.7150/jca.11959. Available from http://www.jcancer.org/v06p1114.htm
Deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is well known in many hematologic malignancies, but only few reports have investigated this deletion effect on clinical prognosis. This study performed analysis of the CDKN2 deletion in 215 adult B- lineage acute lymphoblastic leukemia (B-ALL) patients, and related cytogenetic prognostic factors (BCR/ABL; E2A/PBXl; TEL/AML1; Mixed Lineage Leukemia (MLL) rearrangement; MYC, Immunoglobulin heavy locus (IGH) translocation). The prevalence of CDKN2 deletions in all study populations was 28.4%. There is no difference between patients with CDKN2 deletion and wild-type patients in sex, age, white blood cells (WBC) count, BM blast percentage, extra infiltration and induction complete remission (CR) rate. Analysis in relapse patients revealed that the distribution of CDKN2 deletion is higher in relapse patients (44.6%) than all patients (28.4%, P=0.006). Deletion of CDKN2 was significantly associated with poor outcomes including decreased overall survival (OS) (P<0.001), lower disease free-survival (DFS) (P<0.001), and increased cumulative incidence of relapse (P=0.002); Also, CDKN2 deletion was strongly associated with IGH translocation (P=0.021); and had an adverse effect on patients with BCR-ABL fusion gene or with MLL rearrangement. Patients with CDKN2 gene deletion benefited from allogenic hematopoietic stem cell transplantation (Allo-HSCT). Deletion of CDKN2 gene was commonly observed through leukemia progression and was poor prognostic marker in long-term outcomes.
Keywords: CDKN2, Acute lymphoblastic leukemia, Stem cell, Deletion.