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Acute Myeloid Leukemia (AML)

Upregulation of BAALC/MN1/MLLT11/EVI1 Gene Cluster Relate With Poor Overall Survival and a Possible Linkage With Coexpression of MYC/BCL2 Proteins

Akhter, Ariz PhD*; Farooq, Fahad BSc*; Elyamany, Ghaleb MD*; Mughal, Muhammad K. PhD*; Rashid-Kolvear, Fariborz MD*; Shabani-Rad, Meer-Taher MD*; Street, Lesley MD; Mansoor, Adnan MD, FRCPC*

Applied Immunohistochemistry & Molecular Morphology: August 2018 - Volume 26 - Issue 7 - p 483–488
doi: 10.1097/PAI.0000000000000452
Research Articles

Background: Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice.

Method: In a defined subset (MYC+/BCL2+ or MYC/BCL2) of AML patients (n=20), we examined expression signature of several genes (n=12) of established prognostic value in AML. RNA expression and MYC/BCL2 protein pattern was correlated with 3 cytogenetic risk groups and overall survival.

Results: K-means++ unsupervised clustering defined 2 distinct groups with high and low transcript levels of BAALC/MN1/MLLT11/EVI1/SOCS2 genes (>2.5-fold difference; P<0.001). This mRNA signature trended with higher prevalence of MYC/BCL2 coexpression (P<0.057) and poor overall survival (P<0.036), but did not correlate with conventional cytogenetic risk groups (P<0.084).

Conclusions: This pilot study provides useful data, which may help further refine the prognostic scheme of AML patients outside conventional cytogenetic risk groups. It also presents some biological rationale for future studies to explore the use of novel agents targeting MYC and/or BCL2 genes in combination with conventional chemotherapy protocols for AML.

Departments of *Pathology and Laboratory Medicine, Division of Hematology and Transfusion Medicine, Calgary Laboratory Services, Foothills Medical Centre

Medicine, Division of Hematology and Hematological Malignancies, University of Calgary, Calgary, AB, Canada

A.A. conducted research, reviewed patient clinical data, performed statistical analyses, and wrote manuscript. F.F., G.E., and M.K.M. organized pathology and clinical data, and provided assistance in data analysis/graphics. L.S. assisted in clinical data collection, manuscript writing, and editing. F.R.K. performed cytogenetic review and assisted in manuscript writing/editing. M.-T.S.-R. performed research and assisted in editing the manuscript. A.M. designed and conducted research, performed statistical analyses, and edited the final manuscript.

Supported by research grants from Alberta Cancer Foundation (grant # 25999) and Calgary Laboratory Services (grant # RS-16-600).

The authors declare no conflict of interest.

Reprints: Adnan Mansoor, MD, FRCPC, Department of Pathology and Laboratory Medicine, Division of Hematology and Transfusion Medicine, Calgary Laboratory Services, Room C614, Foothills Medical Centre, University of Calgary, 6th Floor Main Building, 1403-29th St NW, Calgary, AB, Canada T2N 2T9 (e-mail:

Received June 28, 2016

Accepted August 26, 2016

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