Acute Myeloid Leukemia (AML) is a heterogeneous disorder characterized by the accumulation of acquired genetic alterations in hematopoietic progenitor cells that alter normal mechanisms of self-renewal, and differentiation. Once a rapidly and life fatal disease, the prognosis of AML has improved in the past decades. Recurrent cytogenetic and molecular genetic abnormalities are proven to be of diagnostic and therapeutic value. All cases of AML cannot be explained by the low resolution cytogenetic techniques or biased molecular genetic approaches. Recent advancements in high resolution genomic techniques has allowed detection of additional submicroscopic abnormalities in the AML genome. This study set out to determine the copy number alterations (CNAs) in bone marrow and oral epithelial samples from 08 AML cases by whole genome Single Nucleotide Polymorphism (SNP) genotyping using Illumina OmniExpress-12 v1-1 Bead Chips containing 700,000 SNPs. Additionally, using a targeted approach with TaqMan real-time quantitative polymerase reaction (RT-qPCR), we tested for previously reported SNP (rs11554137) in a group of 47 AML patients.

The group of patients comprised of AML-M1 (n=1), M2 (n=5), M4 (n=1) and M5 (n=1), SNP genotyping data analysis identified 13 acquired CNAs in 05 out 08 AML patients. Deletions were more common than amplifications. These CNAs were distributed across all FAB subtypes except AML-M3.AML-M4 subtypes were found to have more CNAs compared to other subtypes. Notably, in three AML-M2 cases4q24 microdeletion was identified. This region spans TET2 gene which is has been shown to cause microdeletions and copy-neutral loss of heterozygosity (LOH) in a patient with diverse myeloid malignancies. Oral epithelial cells from the same patients were negative for the CNAs. Moreover, the 47 patients tested for known SNPs, 4 patients (8.5%) were found positive for rs11554137. SNP (rs11554137) has been reported to be of prognostic importance for overall survival (OS).

The results from this study shows CNAs in regions implicated in myeloid malignancies. The use of high-resolution genomic array identified significant number of CNAs and SNPs which were not previously documented in AML patients in Pakistani population. Further studies dissecting out their role in AML pathogenesis are required.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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