High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients

• Published in: Indian journal of hematology & blood transfusion Vol. 39; no. 3; pp. 376 - 382
• Main Authors: El Zaiat, Reham S., Nabil, Reem, Khalifa, Khaled A., El Feshawy, Aliaa A.
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.07.2023; Springer Nature B.V
• Subjects: Blood Transfusion Medicine; Bone marrow; Hematology; Human Genetics; Leukemia; Medical prognosis; Medicine; Medicine & Public Health; Oncology; Original; Original Article; Hedgehog signaling; GLI-1; FLT3; Acute myeloid leukemia; APL
• ISSN: 0971-4502; 0974-0449; 0974-0449; 0971-4502
• DOI: 10.1007/s12288-022-01609-y

Purpose: To explore the expression and prognostic significance of Hedgehog signaling transcription factor GLI-1 in newly diagnosed acute myeloid leukemia (AML) patients. Methods: Clinical specimens were obtained from 46 recently diagnosed AML patients. Real-time qPCR was used to measure the GLI-1 mRNA expression in bone marrow mononuclear cells.Also, the relationship between GLI-1 mRNA levels and clinical variables and prognostic variables was assessed. Results: GLI-1 was overexpressed in the bone marrow samples of our patients. GLI-1mRNA expression did not differ significantly across different age groups, between both sexes, or between different FAB subtypes (P = 0.882, P = 0.246, and P = 0.890, respectively). GLI-1 expression varied significantly in different risk categories, with the greatest levels observed in 11 patients with poor risk (24.6 versus 22.7) compared to intermediate risk (5.2 versus 3.9; P = 0.006) and favorable risk (4.2 versus 3; P = 0.001). Comparing patients with the wild FLT3 allele to those with the mutant one, GLI-1 gene levels were considerably greater in those with the mutant allele of FLT3.Following induction chemotherapy, the levels of GLI-1 mRNA were significantly higher in 22 patients who did not experience complete remission (CR) diagnosed with de novo non-acute promyelocytic leukemia (APL) compared to 17 patients who did (P = 0.017). Significantly greater levels of expression were observed in each category of the patients with favorable risk; wild FLT3 allele (P = 0.033) and CR failure P = 0.005). Conclusion: GLI-1 overexpression is a risk factor for poor prognosis and could be a novel therapeutic target for AML.