Research ArticlesDe Novo Acute Myeloid Leukemia in Adults Suppression of MicroRNA-223 is Independent of LMO2 Protein Expression BUT Associate With Adverse Cytogenetic Profile and Undifferentiated Blast MorphologyAkhter, Ariz PhD*; Patel, Jay L. FRCPC*; Farooq, Fahad BSc*; Qureshi, Abid BSc*; Taher-Rad, Meer-Shahbani FRCPC*; Elyamany, Ghaleb FRCPC†; Al-Zahrani, Ali M. FRCR†; Rashid-Kolvear, Fariborz PhD‡; Mansoor, Adnan FRCPC*Author Information *Calgary Laboratory Services (CLS), Department of Pathology & Laboratory Medicine, Division of Hematology & TM ‡Calgary Laboratory Services (CLS), Department of Pathology & Laboratory Medicine, Division of Anatomic Pathology, University of Calgary, Calgary, AB, Canada †Department of Pathology and Laboratory Medicine (GE) and Oncology (AMA), Prince Sultan Military Medical City, Riyadh, Saudi Arabia Supported by Alberta Cancer Foundation Grant #25999. The authors declare no conflict of interest. Reprints: Adnan Mansoor, FRCPC, Rm C614; Foothills Medical Centre, 6th Floor Main Building, 1403-29th St NW, Calgary, AB, Canada T2N2T9 (e-mail: [email protected]). Received June 26, 2014 Accepted August 23, 2014 Applied Immunohistochemistry & Molecular Morphology: November/December 2015 - Volume 23 - Issue 10 - p 733-739 doi: 10.1097/PAI.0000000000000145 Buy Metrics Abstract MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients. In this study, we examined the expression of MIR223 in a large cohort of AML patients and correlated it with LMO2 protein expression, cytogenetic data, degree of differentiation [French-American and British (FAB)/World Health Organization classifications], and overall survival. MIR223 expression was upregulated in only a subset of patients (37%). Suppression of MIR223 was more frequent among patients with aneuploid karyotype compared with diploid karyotype (P=0.005). In AML, not otherwise specified category, AML with maturation (FAB-M2) showed higher levels of MIR223 when compared with either AML without maturation (FAB M0/M1) (P=0.001); AML with monoblastic differentiation (FAB M4/M5) (P=0.004) or AML with myelodysplasia-related changes (P=0.011). Among cytogenetic risk groups, suppression of MIR223 was universal (>95%) in high-risk group when compared with intermediate-risk group (P=0.004). No correlation between MIR223 and LMO2 protein expression was identified. In conclusion, we have shown that suppression of MIR223 expression, as compared with controls, is associated with lack of differentiation and adverse cytogenetic profile, but unrelated with LMO2 protein expression or overall survival. Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.