AUTHOR=Zhang Jingying , Xu Xiao-Jun , Liu Lixia , Song Hua , Shen Heping , Xu Weiqun , Zhao Fenying , Liang Juan , Liao Chan , Wang Yan , Xia Tian , Cao Shanbo , Tang Yongmin , Qin Jiayue , Shen Diying 

TITLE=Clinical and Genetic Characteristics of IKZF1 Mutation in Chinese Children With B-Cell Acute Lymphoblastic Leukemia

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.822832

DOI=10.3389/fgene.2022.822832

ISSN=1664-8021

ABSTRACT=<p>Acute lymphoblastic leukemia (ALL) is a malignancy associated with altered lymphoid precursor hyperplasia and accompanied with different genetic mutations. Few studies have been reported on the association between gene mutations and clinical features of <italic>IKZF1</italic> mutation in children with B-cell ALL (B-ALL). We investigated clinical and genetic characteristics in 200 newly diagnosed pediatric B-ALL through multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) method. We found that <italic>IKZF1</italic> mutations, including large segment deletions, small insertions or deletions (InDels) and single nucleotide variations (SNVs), were detected in 22 patients with a positive mutation rate of 11.0%. <italic>IKZF1</italic> mutation was significantly associated with higher WBC count (19.38 × 10<sup>9</sup>/L vs. 5.80 × 10<sup>9</sup>/L, <italic>p</italic> = 0.002). Compared with <italic>IKZF1</italic> wild-type cases, a higher frequency of <italic>IL7R</italic> gene mutation was discovered in <italic>IKZF1</italic> mutant cases (9.1% vs. 0.0%, <italic>p</italic> = 0.012). Patients with <italic>IKZF1</italic> mutation were less sensitive to glucocorticoid induction than patients without <italic>IKZF1</italic> mutation (63.6% vs. 9.0%, <italic>p</italic> &lt; 0.001). On the 15th day of induction, minimal residual disease (MRD) &gt; 10<sup>−3</sup> level were higher in <italic>IKZF1</italic> mutant patients than wild-type patients (45.5% vs. 22.3%, <italic>p</italic> = 0.018). In conclusion, our study reveals the association between genetic mutations and clinical features in Chinese children with B-ALL, which might contribute to molecular classification, risk stratification and prognosis evaluation, and provide new ideas for targeted therapy in ALL.</p>