Common CNAs involved CDKN2A/2B (30.3%), IKZF1 (27.3%), PAX5 (9.1%), RB1 (9.1%), BTG1 (6.7%), and ETV6 (6.7%), which regulate cell cycle, B lymphopoiesis, or act as tumor suppressors in ALL.
<i>CDKN2A/2B</i> deletions were associated with poor 2-year OS (P=0.045) and RFS (P=0.071) rates in Philadelphia chromosome positive (Ph<sup>+</sup>) B-ALL patients, as well as in the high risk (HR) B-ALL group (P=0.037 and P=0.047, respectively).
The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.
The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance.
We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response.
Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL.
These SNPs are located at CDKN2A (rs3731217) and IKZF1 (rs4132601), genes frequently lost in ALL, and at CEBPE (rs2239633), ARID5B (rs7089424), PIP4K2A (rs10764338), and GATA3 (rs3824662), genes located on chromosomes gained in high-hyperdiploid ALL.
Deletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse prognosis for adolescents and adults with B-precursor ALL, and this suggests that these CNAs should be included in the initial risk assessment of ALL.
Notably, the CDKN2A variant was not significantly associated with melanoma, glioblastoma, or pancreatic cancer risk, implying that this polymorphism specifically confers ALL risk but not general cancer risk.
To determine the prevalence and prognostic impact of significant acute lymphoblastic leukemia (ALL) -related genes: CRLF2 deregulation (CRLF2-d), IGH@ translocations (IGH@-t), and deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, and EBF1 in adolescents and adults.
Recent studies have shown that SNPs mapping to 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B), and 14q11.2 (CEBPE) and carrier status for recessively inherited Nijmegen Breakage syndrome (NBS) influence childhood acute lymphoblastic leukemia (ALL) risk.
We hypothesized that this association reflects the capability of some ANRIL polymorphisms to contribute to its transcription changes responsible for alterations of CDKN2A/B expression profiles, thus leading to abnormal proliferative boosts and consequent increased ALL susceptibility.