TY - JOUR
T1 - Chromosomal Instability in Chronic Myeloid Leukemia
T2 - Mechanistic Insights and Effects
AU - Senapati, Jayastu
AU - Sasaki, Koji
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - The most recent two decades have seen tremendous progress in the understanding and treatment of chronic myeloid leukemia, a disease defined by the characteristic Philadelphia chromosome and the ensuing BCR::ABL fusion protein. However, the biology of the disease extends beyond the Philadelphia chromosome into a nebulous arena of chromosomal and genetic instability, which makes it a genetically heterogeneous disease. The BCR::ABL oncoprotein creates a fertile backdrop for oxidative damage to the DNA, along with impairment of genetic surveillance and the favoring of imprecise error-prone DNA repair pathways. These factors lead to growing chromosomal instability, manifested as additional chromosomal abnormalities along with other genetic aberrations. This worsens with disease progression to accelerated and blast phase, and modulates responses to tyrosine kinase inhibitors. Treatment options that target the genetic aberrations that mitigate chromosome instability might be a potential area for research in patients with advanced phase CML.
AB - The most recent two decades have seen tremendous progress in the understanding and treatment of chronic myeloid leukemia, a disease defined by the characteristic Philadelphia chromosome and the ensuing BCR::ABL fusion protein. However, the biology of the disease extends beyond the Philadelphia chromosome into a nebulous arena of chromosomal and genetic instability, which makes it a genetically heterogeneous disease. The BCR::ABL oncoprotein creates a fertile backdrop for oxidative damage to the DNA, along with impairment of genetic surveillance and the favoring of imprecise error-prone DNA repair pathways. These factors lead to growing chromosomal instability, manifested as additional chromosomal abnormalities along with other genetic aberrations. This worsens with disease progression to accelerated and blast phase, and modulates responses to tyrosine kinase inhibitors. Treatment options that target the genetic aberrations that mitigate chromosome instability might be a potential area for research in patients with advanced phase CML.
KW - additional cytogenetic abnormalities
KW - chromosomal instability
KW - CML
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U2 - 10.3390/cancers14102533
DO - 10.3390/cancers14102533
M3 - Review article
C2 - 35626137
AN - SCOPUS:85130226291
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 10
M1 - 2533
ER -