TITLE:
The Impact of miRNA-155 Expression on Treatment Outcome in Adult Acute Myeloid Leukemia Patients
AUTHORS:
Tarek Elgohary, Fouad Abu-Taleb, Rania Ghonaim
KEYWORDS:
miR-155, Micro-RNA, AML
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.10 No.3,
February
28,
2019
ABSTRACT: Background: Acute myeloid leukemia
is a heterogeneous hematologic malignancy associated with gene mutations,
chromosomal rearrangements, deregulation of gene expression and epigenetic
modifications. The treatment outcome of AML is highly variable
signifying the heterogeneous nature of the disease. Aim of the Study: To evaluate miRNA-155 expression
level as a prognostic marker for adult patients with acute myeloid leukemia. Patients
and Methods: 101 subjects were included in this study. They were classified
into 2 groups, patient group (61 adult patients with newly diagnosed acute
myeloid leukemia) and control group (40 apparently healthy adult subjects). miRNA-155 expression
was assessed using real time PCR using QIAGEN, miScript, Quanti Tect and Rotor-isc (QIAGEN
Group) PAXgene (pre Analytix Gmbh). Samples were either peripheral blood or bone
marrow aspiration sample. Results: Roc curve detected 2.85 as best fit
value of miRNA-155 for discriminating patients from healthy controls with
sensitivity 92.3%, specificity 88.5%, AUC 0.98 and CI (0.96 - 0.99) (p th percentile value of the patient group was taken as prognostic cut off value with a value The expression level
of miRNA-155 was significantly higher in AML patients than in controls (p =
0.002). Patients with high miRNA expression had a significantly higher white blood cells count (p = 0.002),
bone marrow blasts (p = 0.006) and peripheral blood blasts (p = 0.006) compared
to patients with low miRNA-155 expression. Patients with poor cytogentics had a significantly
higher level of miRNA-155 expression compared to patients with favorable
cytogentics (p = 0.007). The complete remission rate was significantly higher
in patients with low miRNA-155 expression compared to those with high
expression (86.4% and 23.5%, consequently, p = 0.004). The disease free
survival was significantly shorter in patients with high miRNA-155 expression
compared to those with low expression (median 12 months, 95% CI (7.4 - 15.5)
and median notreached, consquenly, p = 0.001). The overall survival was
significantly higher (p =
0.002) in patients with low miRNA-155 expression (median overall survival was
not reached) compared to patients with high miRNA-155 expression (median
overall survival 14.5 months, 95% CI; 10.2 - 17.6). Conclusion: The
expression level of miR-155 was significantly higher in AML patients than in
control groups and high miRNA-155 expression level was significantly associated
with poor cytogenetics, poor response to therapy and shorter disease free
and overall survival conferring a poor outcome.