The expression of early embryonic stem cell transcription factors in leukemic stem cells

Transcriptional factors such Oct-4, Nanog and Rex-1 have pivotal role in self-renewal, differentiation and pluripotency of the embryonic stem cells (ESC). In terms of self reneval, unlimited proliferation, differentiation and invasion, cancer cells and embryonic stem cells display similar phenotypic properties. This analogy implies that cancer cells may re-express some of the early ESC transcriptional factors. A couple of studies have revealed expression of early embryonic transcriptional factors on normal adult stem cells and some human cancer cell types. However, expression of early embryonic transcriptional factors has not studied in hematopoietic stem cells and myeloid leukemia cell lines, yet.In this study, we was carried out to investigate the expression of early embryonic transcriptional factors in stem cells of healthy controls, acute myeloid leukemia (AML), chronic myeloid leukemia (CML) by real time reverse transcription polymerase chain reaction (RT-PCR) and flow cytometric analysis.Our results showed that some samples of CD34 positive cell fractions from cases of both control and leukemic groups were negative for RT-PCR mediated Oct-4, Nanog and Rex-1 amplification. However, positive amplification was observed in all CD34 negative cells obtained from healthy volunteers and patients with AML or CML. Nonetheless, relative quantitative expression levels of these factors in these patient groups were lower than healthy volunteers. On the other hand, subgroup analysis revealed that Oct-4 and Nanog expressions were higher in patients with minimally differentiated AML (M1 phenotype according to FAB classification) than healthy controls and those patients with other leukemia types. Flow cytometric analysis of the CD34 negative cell fraction was also revealed moderately high expression levels. This finding was concordant with molecular studies.In conclusion, in this pioneering study we have demonstrated that early ESC transcriptional factors were expressed by different cell fractions obtained from healthy controls and leukemic cells to some extend. The expression is interestingly founded in the CD34 negative compartment of the stem cells (non-hematopoietic stem cells). The most remarkable finding was the high Oct-4 and Nanog transcript levels of cell fractions of patients with acute myeloid leukemia without maturation (AML FAB M1) as indicating immaturity. Regarding our results, investigation of these embryonic transcription factors may help to determine the leukemic transformation step. Moreover, development of targeted therapies against these transcriptional factors may be a therapeutic approach in the near future.Keywords: Oct-4, Nanog, Rex-1, SSEA.4, Leukemic stem cell, AML, CML