A meta-analysis of the prognostic significance of CDKN deletions in acute lymphoblastic leukaemia

Ann Med. 2024 Dec;56(1):2427365. doi: 10.1080/07853890.2024.2427365. Epub 2024 Nov 18.

Abstract

Background: B-cell acute lymphoblastic leukaemia (B-ALL) and T-cell acute lymphoblastic leukaemia (T-ALL) are both types of acute lymphoblastic leukaemia (ALL), which is a cancer of the blood and bone marrow characterized by the rapid proliferation of immature lymphocytes. In ALL, CDKN gene deletions have been extensively studied regarding their prognostic significance. The purpose of this meta-analysis is to determine whether there is a consistent relationship between CDKN gene variations and the incidence of lymphocytic leukaemia.

Materials and methods: The following databases contain relevant studies published between inception and 25 October 2023: PubMed, EMBASE, the Cochrane library and Web of Science were comprehensively searched. Based on the random-effects or fixed-effects model, the hazard ratio (HR) and its 95% confidence interval (95% CI) were pooled. A subgroup analysis and sensitivity analysis were also conducted. We estimated publication bias using a funnel plot.

Results: This meta-analysis included 19 studies containing 1333 patients. Among included studies, 12 studies only reported B-ALL, four studies included patients with T-ALL and B-ALL, and three studies reported T-ALL. A deletion of the CDKN gene was found to be an adverse indicator of both EFS (HR = 1.83, 95% CI: 1.03-2.62), DFS (HR = 1.49, 95% CI 1.23-1.77), RFS (HR = 1.34, 95% CI 0.96-1.73) and OS (HR = 1.39, 95% CI 1.19-1.58). Single-arm emphasized the greater influence on OS. The subgroup analysis based on the CDKN2A, CDKN2A/b and different ALL subtypes further strengthen the validity of the findings.

Conclusions: Our meta-analysis revealed that CDKN gene deletions (including CDKN 2A/B, CDKN 2A) serve as adverse prognostic indicators for T-ALL/B-ALL patients.

Keywords: Acute lymphoblastic leukaemia; CDKN gene; meta-analysis.

Plain language summary

Acute lymphoblastic leukaemia is a complex hematologic malignancy, requiring precise risk stratification to tailor treatment regimens for individual patients.Due to their prognostic significance in acute lymphoblastic leukaemia (ALL), CDKN gene deletions have been the subject of extensive research.Based on the results of this meta-analysis, CDKN gene deletions are potential adverse prognostic indicators for T-cell acute lymphoblastic leukaemia (T-ALL)/B-cell acute lymphoblastic leukaemia (B-ALL) patients.

Publication types

  • Meta-Analysis

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p15* / genetics
  • Cyclin-Dependent Kinase Inhibitor p16* / genetics
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Gene Deletion*
  • Humans
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prognosis

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p21
  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • CDKN1B protein, human
  • Cyclin-Dependent Kinase Inhibitor p18