Combined analysis of IKZF1 deletions and CRLF2 expression on prognostic impact in pediatric B-cell precursor acute lymphoblastic leukemia

Abstract

This study aimed to investigate the combined impact of IKZF1 deletions/high expression of CRLF2 on the prognosis of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 deletions and CRLF2 expression were assessed in bone marrow samples from 117 children with newly diagnosed BCP-ALL. Sixteen (13.7%) patients were found to harbor IKZF1 deletions, which was associated with inferior outcomes. The event-free survival (EFS) for patients with high -CRLF2 expression was significantly worse than that for low -CRLF2 expression. Moreover, combined modeling of IKZF1⁺/CRLF2^high identified 7.8% of cases as the highest risk subgroup (7-year EFS 33.3 ± 15.7%). In a multivariate analysis, IKZF1⁺/CRLF2^high remained a strong independent prognostic factor for EFS (HR: 14.263, p = 0.019). IKZF1 deletions and high -CRLF2 expression were associated with inferior outcomes, and the coexistence of IKZF1⁺/CRLF2^high had a significant impact on an integrated prognostic model for high-risk BCP-ALL.

Keywords:

• Acute lymphoblastic leukemia
• CRLF2
• IKZF1
• prognosis

Acknowledgments

The authors would like to thank all staff members in the hematology oncology center and in the laboratory of hematologic diseases who have taken care of the patients and given the help for the studies.

Disclosure statement

All authors declare that they have no conflicts of interest to disclose.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [No. 81970135 and 81870114], the Beijing Municipal Science & Technology Commission [No. Z181100001718100], the Beijing Natural Science Foundation of China [No. 7202044]; the Scientific Research Common Program of Beijing Municipal Commission of Education [No. KM201810025025] and New Sunshine Charity Foundation, China [No. 2017002].