Publication details

Methylation of histone H3K9 in human blood cells and in granulocytes of patients with myeloid leukemia

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Year of publication 2004
Type Article in Proceedings
Conference Biophysics of the Genome
MU Faculty or unit

Faculty of Informatics

Field Genetics and molecular biology
Keywords cytometry
Description We show that common heterochromatin antigenic protein markers (HP1alpha, beta, gamma, mono-, di-, and tri-methylated histone H3K9), while present in human blood progenitor CD34+ cells, differentiated lymphocytes and monocytes, are absent in neutrophile granulocytes and, to large extent, in eosinophiles. Mono-methylated and, in particular, di-methylated H3K9 are present to variable degrees in the granulocytes of CML patients, without being accompanied by HP1 proteins. In patients with an acute phase of CML and in AML patients, strong methylation of H3K9 and all isoformes of HP1 are detected. In chronic forms of CML, no strong correlations among the level of histone methylation, disease progression and modality of treatment were observed. Histone methylation was found even in cured patients without BCR/ABL translocation, suggesting an incomplete process of developmentally-regulated chromatin remodeling in the granulocytes of these patients. Similarly, reprogramming of leukemia HL-60 cells to terminal differentiation by retinoic acid does not eliminate H3K9 methylation and the presence of HP1 isoformes from differentiated granulocytes. Thus our study shows for the first time that histone H3 methylation may be dramatically changed during normal cell differentiation. The residual histone H3 methylation in myeloid leukemia cells suggests an incomplete chromatin condensation that may be linked to the leukemia cell proliferation and may be important for the prognosis of disease treatment and relapse.
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