AML M3 and AML M3 variant each have a distinct gene expression signature but also share patterns different from other genetically defined AML subtypes
Torsten Haferlach, Alexander Kohlmann, Susanne Schnittger, Martin Dugas, Wolfgang Hiddemann, Wolfgang Kern, Claudia Schoch. Genes, Chromosomes, and Cancer, 43(2): 113-127.
Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), can be divided into two distinct subtypes: AML M3 and AML M3v. AML M3 has abnormal promyelocytes with heavy granulation and bundles of Auer rods while AML M3v shows non- or hypogranular cytoplasm and a bilobed nucleus. Patients with M3 and M3v subtypes often suffer severe bleeding that causes early death. Identification of differentially expressed signature genes in these two subtypes will help to understand the morphological features associated with development, along with clinical differences in the diseases they cause.
A global expression profile of bone marrow aspirates from 35 APL patients (19 AML M3 and 16 AML M3v) was generated using the Affymetrix7 GeneChip7 U133 array sets. Clustering analysis of expression patterns revealed that the APL samples were grouped distinctly from other AML subtypes and karyoptype. In addition, specific gene expression signatures correlated with coagulation in APL compared to other AML subtypes. Thirteen genes were identified that differed in expression patterns between M3 and M3v subtypes. The findings were validated by real time PCR.
IPA software and the Ingenuity Knowledge Base were applied for further analysis and confirmation of biological pathways and functional networks. Figure 2 in this paper shows a biological network distinguishing APL from other AML. A network also confirmed a known finding in which genes relevant to MHC-II antigen presentation are expressed less in APL. Another significant biological network, displayed in Figure 6 revealed that genes involved in clotting/coagulation were highly expressed in APL but not in other AML subtypes.
Other genes involved in maturation, granulation and nuclear configuration were also identified from functional networks. The DEFA gene was highly expressed in primary granules (APL M3) while the TCN2 gene was overexpressed in secondary granules (APL M3v). Importantly, this was the first example of discrimination between APL subtypes at the transcriptome level. |
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