Expression profiling of microarray gene signatures in acute and chronic myeloid leukaemia in human bone marrow

Classification of cancer subtypes by means of microarray signatures is becoming increasingly difficult to ignore as a potential to transform pathological diagnosis; nonetheless, measurement of Indicator genes in routine practice appears to be arduous. In a preceding published study, we utilized real-time PCR measurement of Indicator genes in acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML) as a way of application of microarray gene signatures. More to the point, the specificity of such genes for this distinction was investigated by their measurement in cases afflicted with chronic myeloid leukaemia (CML) and with normal bone marrow (BM).

Mononuclear cells were sorted into unselected (total), CD34+ve, and CD34-ve fractions, mRNA globally amplified by using PolyA PCR. Moreover, the level of expression of 17 Indicator genes was identified by using real-time PCR.

No statistically significant difference was observed in expression for any gene among CML cases. Cyclin D3 (p≤0.04) was exclusively upregulated in CML in the CD34+ fraction, notwithstanding upregulation of HkrT-1 (p≤0.02) and fumarylacetoacetate (p≤0.03) in AML. HOXA9 experienced a non-significant upregulation in AML; however, in combination with proteoglycan 1 distinguished between AML and normal samples in the CD34- fraction in unsupervised clustering. Unsupervised clustering distinguished among AML and the other diagnostic groups.

The evidence from the present study suggests that the genes discriminatory between ALL and AML are uninformative in the context of CML and normal BM, excepting for distinction with AML.