Advances in Pharmacology and Pharmacy Vol. 1(2), pp. 88 - 94
DOI: 10.13189/app.2013.010207
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The Mechanism by which Chronic Myeloid Leukemia Responds to Interferon-α Treatment


Emad Y. Moawad*
Dept. of Engineering, Ain Shams University, Cairo, Egypt

ABSTRACT

The goal of this work is to determine the mechanism by which addition of interferon-α (IFN-α ) to Dendritic Cells (DC) grown from Chronic Myeloid Leukemia (CML) patients improves its capacity to stimulate T-lymphocyte responses, and decreases the proportion of bcr-abl positive DC. Bone marrow samples were obtained from six patients with CML and six normal donors to prepare mononuclear cells. T lymphocytes were removed, cultured without IFN-α (control sample) and with IFN-α doses of 5, 50, 250, and 500 U/mL. After a culture period of 14 days, DC were harvested and added to freshly allogeneic T cells by a ratio 1:10 for Mixed Lymphocyte Reaction (MLR) assay to identify energy of those mixed cultures (EMLR). Fluorescence in situ hybridization (FISH) was performed to quantify the frequency of bcr-abl in fresh samples from newly diagnosed CML patient with cultured DC without IFN-α and with IFN-α dose of 250 U/mL. Variations in EMLR of mixed cultures were attributed to each of the difference in energy of the cultured DC (EDC) obtained from IFN-αdoses, and either of rising the histologic grade (HG) of those cultures due to cell cycle arrest (ECCA) that cause treatment failure or reducing HG due to energy released by the loss of mitochondrial membrane potential (Ψmito ) activating apoptosis in bcr-abl positive cells. Percentage of decrease in bcr-abl positive DC in FISH analysis was 100% identical to that in each of EDC and Ψmito (p≤0.001). Patient-specific approaches that account for HG variations should enable more accurate dose estimates. IFN-α therapy is an energy balance process in which CML cells respond according to the mechanism of the following model: EMLR=HG + EDC & ECCA or Ψmito = Abs (HG.Control-HG).

KEYWORDS
Dendritic cells, IFN-α , Histologic grade, bcr/abl oncogene, Apoptosis, Mitochondria

Cite this paper
Emad Y. Moawad . "The Mechanism by which Chronic Myeloid Leukemia Responds to Interferon-α Treatment." Advances in Pharmacology and Pharmacy 1.2 (2013) 88 - 94. doi: 10.13189/app.2013.010207.