Cancers, Vol. 12, Pages 903: Role of DNA Damage Response in Suppressing Malignant Progression of Chronic Myeloid Leukemia and Polycythemia Vera: Impact of Different Oncogenes
Cancers, Vol. 12, Pages 903: Role of DNA Damage Response in Suppressing Malignant Progression of Chronic Myeloid Leukemia and Polycythemia Vera: Impact of Different Oncogenes
Cancers doi: 10.3390/cancers12040903
Authors:
Jan Stetka
Jan Gursky
Julie Liñan Velasquez
Renata Mojzikova
Pavla Vyhlidalova
Lucia Vrablova
Jiri Bartek
Vladimir Divoky
Inflammatory and oncogenic signaling, both known to challenge genome stability, are key drivers of BCR-ABL-positive chronic myeloid leukemia (CML) and JAK2 V617F-positive chronic myeloproliferative neoplasms (MPNs). Despite similarities in chronic inflammation and oncogene signaling, major differences in disease course exist. Although BCR-ABL has robust transformation potential, JAK2 V617F-positive polycythemia vera (PV) is characterized by a long and stable latent phase. These differences reflect increased genomic instability of BCR-ABL-positive CML, compared to genome-stable PV with rare cytogenetic abnormalities. Recent studies have implicated BCR-ABL in the development of a "mutator" phenotype fueled by high oxidative damage, deficiencies of DNA repair, and defective ATR-Chk1-dependent genome surveillance, providing a fertile ground for variants compromising the ATM-Chk2-p53 axis protecting chronic phase CML from blast crisis. Conversely, PV cells possess multiple JAK2 V617F-dependent protective mechanisms, which ameliorate replication stress, inflammation-mediated oxidative stress and stress-ac...
Source: Cancers - Category: Cancer & Oncology Authors: Jan Stetka Jan Gursky Julie Li ñan Velasquez Renata Mojzikova Pavla Vyhlidalova Lucia Vrablova Jiri Bartek Vladimir Divoky Tags: Review Source Type: research