The Involvement of Oxidative Stress in Chronic Myeloid Leukemia

Abstract

In the past decades, the involvement of reactive oxygen species (ROS) in health and disease has been intensely studied. Apart from their antimicrobial role in phagocytosis, ROS are also involved in a multitude of cellular processes, such as cell cycle progression, cellular motility or amplification of signaling factors. Many diseases are characterized by an overproduction of ROS or by deficient antioxidant systems, thus leading to oxidative stress (OxS) onset. The involvement of OxS in several types of solid cancers (prostate cancer, breast cancer, colorectal cancer and melanoma) and hematological malignancies (acute lymphoblastic leukemia, myelodysplastic syndromes, acute and chronic myeloid leukemia) has been proved. Recent studies have hypothesized that ROS derived from tumors can promote cell survival, migration, metastasis, proliferation and even drug-resistance according to the origin of the cancer. However, the involvement of OxS in carcinogenesis is far from being completely understood.

Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells

“…The role of OS in the progression of hematopoietic malignancies (including CML, AML) has been well documented but is still not fully understood. 31 Our results remain inconsistent with the data published by Barnett et al 15 who showed that supernatants of long-stored (unfiltered and filtered) PRBC increased proliferation and migration of mouse pancreatic cancer cells (Pan02), and when administered intravenously contributed to pancreatic cancer progression in mice. The inconsistency with the obtained results may be related to the use of a completely different line of cancer cells, additionally of mouse origin.…”

Occurrence of chronic myeloid leukemia in a patient with CDC73 gene deletion: “Chance or Causality?”

“…Nevertheless, recent studies report the CDC73 among the genes whose deregulation may play a role in determining the aggressive phenotype of blast crisis CML 9,10 and that reactive oxygen species can promote cancer cell survival and drug resistance. 7 Second, to date, other than the case we described in our paper, only other 13 different large genomic deletions at the CDC73 locus (1q31.2) have been identified. 11,12 In 5 out of 12 cases, the deletion encompasses the whole locus, with the involvement of adjacent genes, while in the remaining ones, the deletion involved only one or more exons.…”

“…First, although it is known that fusion oncogene BCR-ABL1 is essential for CML, the molecular processes underlying its formation is far from being completely understood. Hypothesized mechanisms reporting the role of genome instability induced by oxidative stress 7 or defects in CDC73 8 remain to be further confirmed. Nevertheless, recent studies report the CDC73 among the genes whose deregulation may play a role in determining the aggressive phenotype of blast crisis CML 9,10 and that reactive oxygen species can promote cancer cell survival and drug resistance.…”

Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells

“…Involvement of ROS in the development of chronic myeloid leukemia has been the focus of research for some time [ 34 ]. Earlier research showed elevated levels of ROS production in BCR-ABL1 positive cells when compared to wild-type counterparts [ 35 , 36 , 37 ].…”