Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

Abstract

AML is the most common type of acute leukemia in adults, accounting for approximately 80% of adult cases of acute leukemia. 1 AML is generally recognized as disease of late age, with first-time diagnoses of AML made at 68 years of age on average. 2 Still, children account for 6% to 7% of cases of AML and have a biology that is quite different from that of adult patients. 3The disease arises from bone marrow stem cells which proliferate uncontrollably with impaired differentiation capacity, leading Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. There is growing evidence that microRNAs (miRNAs) provide prognostic information in AML. MiR-204 has a tumor suppressor function, and several studies have proven its role in solid cancers. The aim of this work is to evaluate the level of expression of miR-204 in adults newly diagnosed with AML with normal karyotype and to correlate its level of expression with disease outcome and different prognostic factors. Patients and methods: The study included 87 adult patients newly diagnosed with AML. Detection of miR-204 was done using RT-PCR in patients and seven agematched controls. Results: Acute myeloid leukemia patients showed significantly lower miR-204 expression, compared to control group (P = .029). Low miR-204 expression was significantly associated with positive CD34 (P = .017), with poor performance status (PS) (P = .009), and with the presence of diabetes mellitus (DM) (P = .014). Low expression of miR-204 was also significantly associated with shorter overall survival (OS) (P = .020) and disease-free survival (DFS) (P = .013). Low miR-204 expression was identified as an independent prognostic factor for prediction of shorter OS (P = .034) and DFS (P = .027) in AML. Conclusion: To the best of our knowledge; this is the first time to prove the correlation between miR-204 expression and CD34 expression. Further study of this correlation is needed to confirm the role of miR-204 in CD34-positive cells, including leukemic stem cells. This correlation may have therapeutic implications. MiR-204 can be used as a biomarker for PS in AML patients. K E Y W O R D S acute myeloid leukemia, CD34, leukemic stem cells, miR-204, performance status S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Abdelhafiz AS, Elsayed GM, Saber MM, Gameel A, Hamdy N. Low expression of miR-204 is associated with expression of CD34 and poor performance status in denovo AML. Int J Lab Hematol. 2020;42:263-269.

MicroRNA-1306-5p Regulates the METTL14-Guided m6A Methylation to Repress Acute Myeloid Leukemia

“…Therefore, miRNAs are considered to be natural regulators of gene expression [ 11 ]. Several miRNAs are also found to play crucial roles in AML by regulating various kinds of biological processes, such as miRNA-485-5p, miR-126, and miR-204 [ 12 – 14 ]. In addition, as reported previously, miR-1306-5p is involved in the progression of many diseases, such as amelogenesis imperfecta, cerebral ischemia/reperfusion injury, and sepsis [ 15 – 17 ].…”

Research progress on molecular biomarkers of acute myeloid leukemia

“…After induction chemotherapy, AML patients with upregulated miR-204 had a higher CRR. Therefore, miR-204 is expected to become a biomarker for the prognostic evaluation of AML ( 61 ). Hu et al.…”

Leukemic Stem Cell: A Mini-Review on Clinical Perspectives

“…Table 1 is comprised of clinical trials from the past 10 years that aimed to identify biomarkers specific to LSCs that could serve as targets for targeted therapies or could be used as prognostic factors (89)(90)(91)(92)(93)(94)(95)(96)(97)(98). Most of the reported studies aim at AML treatment since LSC presence and complexity is an established risk factor for disease severity (51,56).…”

“…Studies utilizing standard chemotherapy protocols and induction therapies confirm that identified LSC markers, mainly transmembrane antigens such as CD34 and CD123, correlate with a worse patient prognosis. Increased mutation burden, lower response rates, inability to achieve CR, worst response to chemotherapy and higher incidence of relapse are some of the reported factors associated with increased presence of LSCs (89,(92)(93)(94)96).…”