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Deregulation of many signaling pathways is involved in the onset and progression of different forms of cancers including leukemia,a malignant hematological neoplasm that results in unusual proliferation of white blood cells in the bone marrow.During the course of leukemia,gradual amplification of mutational events at the genetic and/or epigenetic levels are believed to have major knock-on effect in altering and activating the expression of different mitogenic,anti-differentiating and anti-apoptotic modulators,which affect the plasma proteome profiles as well.Analysis of these altered protein profiles in patients and their healthy counterparts are likely to assist in keeping track of the concealed perturbations while expediting the search for novel biomarkers and therapeutic targets of the disease.Two-dimensional gel electrophoresis in conjunction with mass spectrometry has been employed for the identification of biomarkers of chronic-phase chronic myeloid leukemia (CP-CML).Over 1300 plasma protein spots were subjected to analysis by MALDI-TOF mass spectrometry,which resulted in identification of 33 distinct proteins and their respective isoforms/subunits.Comparative analysis revealed differential expression of six proteins which were subsequently confirmed through ELISA with p-value <0.005.Amongst these candidates,three proteins were successfully validated both in the pre-treated and nilotinib-treated CP-CML cases,using quantitative ELISA (ANOVA p=0.0001).Further,a curated pathway of differentially expressed proteins was built up,which seems to translate the probable association of marker proteins with the BCR-ABL-driven genomic instability.