EIF3B Associates with Exacerbated Clinical Features, Poor Treatment Response and Survival in Adult Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Patients

Technol Cancer Res Treat. 2021 Jan-Dec:20:15330338211041464. doi: 10.1177/15330338211041464.

Abstract

Objective: This study was undertaken to investigate eukaryotic translation initiation factor 3 subunit B (EIF3B) expression and its clinical value for indicating disease progression and prognosis in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph- ALL) patients. Methods: Totally, 76 adult Ph- ALL patients and 30 healthy donors (HDs) were included. Bone marrow (BM) samples before therapy (baseline), after 4-week therapy of Ph- ALL patients and the BM samples of HDs were collected. Then, EIF3B expression in BM was detected by reverse transcription quantitative polymerase chain reaction. Results: EIF3B expression was increased in Ph- ALL patients compared with HDs, which distinguished Ph- ALL patients from HDs (area under the curve [AUC]: 0.928; 95% confidence interval [CI]: 0.882-0.974) by receiver operating characteristic curve. Furthermore, higher baseline EIF3B expression was associated with elevated white blood cell and bone marrow blasts, while it was associated with lower complete remission (CR) within 4 weeks and less allogeneic hematopoietic stem cell transplant achievements in Ph- ALL patients. Additionally, higher baseline EIF3B expression was associated with decreased disease-free survival but not overall survival. However, it was associated with raised 1-year mortality and 3-year mortality in Ph- ALL patients. After 4-week therapy, EIF3B expression was reduced in total Ph- ALL patients. Notably, the reduction of EIF3B expression was more obvious in Ph- ALL patients who achieved CR within 4 weeks compared with Ph- ALL patients who did not achieve CR within 4 weeks. Conclusion: EIF3B overexpression is related to worsened clinical features, poor treatment response and survival in adult Ph- ALL patients.

Keywords: adult Philadelphia chromosome negative acute lymphoblastic leukemia; clinical feature; eukaryotic translation initiation factor 3 subunit B; survival profiles; treatment response.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Biomarkers / blood
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage
  • Daunorubicin / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Eukaryotic Initiation Factor-3 / genetics*
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukocyte Count
  • Male
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prednisone / administration & dosage
  • RNA / metabolism
  • ROC Curve
  • Survival Rate
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Biomarkers
  • EIF3B protein, human
  • Eukaryotic Initiation Factor-3
  • Vincristine
  • RNA
  • Cyclophosphamide
  • Asparaginase
  • Prednisone
  • Daunorubicin