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

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.

SUBMITTER: Zhu F

PROVIDER: S-EPMC8511920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.

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

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