HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients

Abstract

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder of hematopoietic , characterized by Philadelphia chromosome containing BCR-ABL fusion gene. The gene encodes protein with constitutive tyrosine kinase activity result in myeloid proliferation and leads to form an early phase of CML called chronic phase. Unsuccessful treatment will lead to progression of the disease into late phase (accelerated and blast crisis). The mechanisms involving disease progression are still poorly understood. It is assumed that additional genetic event involves in differentiation blocking of myeloid progenitor cells, such as Hes-1 overexpression and CEBPA down regulation. However, study on the expression of these genes in CML patient’s samples is still limited. This study aims to measure Hes-1 and CEBPA mRNA in chronic and late phase of CML patients. The peripheral blood mRNA level of Hes-1 was measured in CML patient’s sample with BCR-ABL positive both in chronic phase (n=61) and late phase (n=17) using qRT-PCR with GAPDH as internal control. Hes-1 mRNA was statistically higher (p value=0.0) in the chronic phase (mean ± SD=97.8 ± 236.6) compared to those in late phase (mean ± SD=8.5 ± 30.7). In addition, even though CEBPA expression in chronic and late phase were not statistically different (p value=0.1), those in chronic phase (mean ± SD=5.2 ± 16.0) were generally higher compared to those in late phase (mean ± SD=1.7 ± 2.4). Hes-1 expression upregulated in 70.5% of chronic phase patients and in 17.6% of late phase patients, whereas CEBPA expression down regulated in 42.6% of chronic phase patients and in 47.1% in late phase patients. High standard deviation, particularly in mRNA Hes-1 gene expression measurement of the chronic phase, indicated the presence of individual variations in the sample that might be influenced by other genetic factors. This study found that Hes-1 mRNA is significantly higher in peripheral blood of chronic phase than blast crisis CML, whereas CEBPA mRNA is not different.