Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements

Nadia El Menshawy; Mohamed S El-Ghonemy; Mohamed A Ebrahim; Maryan Waheeb Fahmi; Maha Saif; May Denewer; Shaimaa El-Ashwah

doi:10.1007/s00277-024-05779-9

Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements

Ann Hematol. 2024 May 7. doi: 10.1007/s00277-024-05779-9. Online ahead of print.

Authors

Nadia El Menshawy¹, Mohamed S El-Ghonemy¹, Mohamed A Ebrahim², Maryan Waheeb Fahmi³, Maha Saif², May Denewer⁴, Shaimaa El-Ashwah⁴

Affiliations

¹ Clinical Pathology, Hematology unit, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
² Medical Oncology Unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
³ Medical Oncology Unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt. marianwaheeb@mans.edu.eg.
⁴ Clinical Hematology Unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.

PMID: 38710877
DOI: 10.1007/s00277-024-05779-9

Abstract

Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

Keywords: Acute myeloid leukemia (AML); Ecotropic viral integration site-1 (EVI-1); Myocyte enhancer factor 2 C gene (MEF2C); Prognosis; Transcription.