The roles of DNA epigenetics and clinical significance in Chronic Myeloid Leukemia: a review

Abstract

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22) (q34;q11.2) encoding for the BCR-ABL fusion oncogene. Growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. The significant of therapeutic role in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms. This article focused on the CML and epigenetic and clinical significance. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, cancer, Google scholar, self-experience and PubMed databases. The keywords included leukemia, cancer, illness, epigenetic. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. Current progress in molecular biology and bioinformatics offer novel promising experiments namely as next generation sequencing for new development in epigenetic figures characterization and more understanding of the epigenetic mechanisms to be successfully utilized for personalized CML therapy in the next coming years.

BCR-ABL Independent Mechanisms of Resistance in Chronic Myeloid Leukemia

“…Together, they can directly regulate transcription by acting on DNA damage/repair and DNA replication, modulate RNA levels and stability post-transcriptionally, or have an impact on protein translation or post-translational protein modifications (34). An association between CML progression and resistance to TKI treatment and of CpGs islands was recently demonstrated (35, 36). Moreover, an higher methylation of transcription factor AP-2 alpha (TFAP2A) and early B-cell factor 2 (EBP2) was found in patients with blastic phase with respect chronic phase, and autophagy related 16-like 1 (ATG16L1) was methylated in 69% of CML patients.…”

“…Moreover, an higher methylation of transcription factor AP-2 alpha (TFAP2A) and early B-cell factor 2 (EBP2) was found in patients with blastic phase with respect chronic phase, and autophagy related 16-like 1 (ATG16L1) was methylated in 69% of CML patients. Finally, the probability of achieving a major molecular response (MMR) at 12 or 18 months was lower in methylated with respect to unmethylated cases at baseline (35, 36).…”

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms

“…Epigenetic modifications are reversible and heritable changes that regulate DNA expression while maintaining the same nucleotide sequence [ 189 , 190 , 191 ]. High ROS levels and hypoxic conditions of the BMM lead to DNA damage and ineffective repair, making LSCs prime candidates to undergo genetic evolution.…”

“…Despite having a peak incidence of 15–20% in the general healthy population after the age of 70 [ 8 , 196 , 197 , 198 , 199 ], CHIP is not a cause for CML [ 8 , 21 , 193 ]. However, the concurrent presence of CHIP and leukaemia drives LSC transformation and survival, and is associated with an inferior prognosis [ 8 , 17 , 189 , 195 , 196 , 197 , 198 , 199 ].…”

A review of epigenetic changes in asthma: methylation and acetylation

“…Aberrant epigenetic changes can result in a variety of disorders [ 8 ]. Respiratory diseases like asthma are highly affected by inflammatory gene expression which is correlated with epigenetic mechanisms.…”