MECOM gene overexpression in pediatric patients with acute myeloid leukemia

Authors

  • Mariam Elsherif Department of Pediatric Oncology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt
  • Mahmoud Hammad Department of Pediatric Oncology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Hanafy Hafez Department of Pediatric Oncology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Dina Yassin Department of Clinical Pathology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt; Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Mohamed Ashraf Department of Clinical Pathology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt
  • Nouran Yasser Department of Research, Children’s Cancer Hospital (CCHE), Cairo, Egypt
  • Leslie Lehmann Pediatric Stem Cell Transplantation Unit, Dana Farber Cancer Institute, Boston, MA, USA
  • Alaa Elhaddad Department of Pediatric Oncology, Children’s Cancer Hospital Egypt (CCHE), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt

DOI:

https://doi.org/10.1080/0284186X.2022.2025611

Keywords:

MECOM, pediatric oncology, acute myeloid leukemia

Abstract

Background

Acute myeloid leukemia (AML) is characterized by blocked or aberrant differentiation of hematopoietic stem cells. The MECOM gene overexpression in hematopoietic progenitors induces myeloid differentiation block, resulting in increased self-renewal and survival of these transformed progenitors. However, its exact role in AML remains unclear. We aimed to estimate the prevalence of MECOM overexpression among pediatric AML patients, and assess its impact on clinical outcome.

Patients and Methods

Real-time quantitative polymerase chain reaction and Livak method (2ΔΔCt) were used to determine relative MECOM expression level among 243 pediatric patients with AML. MECOM overexpression was considered if the cumulative relative expression was above 1 (2-ΔΔCt) and was designated as MECOMpos.

Results

Of 243 AML patients tested 57(23.5%) demonstrated MECOMpos. Patients with MECOMpos had significantly lower median age. The frequency of MECOMpos was significantly higher among AML patients with 11q23 abnormalities, complex karyotypes and among high- and intermediate-risk groups compared to low-risk group (p = .014). MECOMpos patients had significantly lower overall survival (OS) (38.7 vs. 78.9%, p < .001), event-free survival (EFS) (37.3% vs. 68.4%, p < .001), and had higher cumulative incidence of relapse (49.5% vs. 23.5%, p = .002) at 36 months compared to MECOMneg patients. Multivariate analysis revealed that MECOMpos was an adverse prognostic factor for OS (hazards ratio (HR) = 2.11, 95% confidence interval (CI) 1.24–3.60, p = .006) and EFS (HR= 1.71, 95% CI 1.07–2.75, p = .025). The logistic regression model showed that MECOMpos was an independent prognostic factor regardless of minimal residual disease status post first induction therapy in the intermediate-risk group (odds ratio 2.89; 95% CI 1.19–6.57, p = .018).

Conclusion

The aberrant MECOM gene expression is an adverse prognostic factor, especially in patients without previously known cytogenetic risk factors. Our results suggest the potential benefit from pretreatment screening for MECOM gene overexpression in newly diagnosed AML patients for better risk stratification and treatment adjustment.

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Published

2022-04-03

How to Cite

Elsherif, M., Hammad, M., Hafez, H., Yassin, D., Ashraf, M., Yasser, N., … Elhaddad, A. (2022). MECOM gene overexpression in pediatric patients with acute myeloid leukemia. Acta Oncologica, 61(4), 516–522. https://doi.org/10.1080/0284186X.2022.2025611

Issue

Vol. 61 No. 4 (2022): Acta Oncologica

Section

Articles