title: De 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 Morphology.
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.
authors.affiliation: *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.
authors.forename: Ariz
authors.initials: A
authors.lastname: Akhter
authors.forename: Jay L
authors.initials: JL
authors.lastname: Patel
authors.forename: Fahad
authors.initials: F
authors.lastname: Farooq
authors.forename: Abid
authors.initials: A
authors.lastname: Qureshi
authors.forename: Meer-Shahbani
authors.initials: MS
authors.lastname: Taher-Rad
authors.forename: Ghaleb
authors.initials: G
authors.lastname: Elyamany
authors.forename: Ali M
authors.initials: AM
authors.lastname: Al-Zahrani
authors.forename: Fariborz
authors.initials: F
authors.lastname: Rashid-Kolvear
authors.forename: Adnan
authors.initials: A
authors.lastname: Mansoor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D060588:LIM Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C085117:LMO2 protein, human; C525067:MIR223, human