AMP-activated protein kinase activation primes cytoplasmic translocation and autophagic degradation of the BCR-ABL protein in CML cells.

ABSTRACT: Chronic myeloid leukemia is driven by the BCR-ABL oncoprotein, a constitutively active protein tyrosine kinase. Although tyrosine kinase inhibitors (TKIs) have greatly improved the prognosis of CML patients, the emergence of TKI resistance is an important clinical problem, which deserves additional treatment options based on unique biological properties to CML cells. In this study, we show that metabolic homeostasis is critical for survival of CML cells, especially when the disease is in advanced stages. The BCR-ABL protein activates AMP-activated protein kinase (AMPK) for ATP production and the mTOR pathway to suppress autophagy. BCR-ABL is detected in the nuclei of advanced-stage CML cells, in which ATP is sufficiently supplied by enhanced glucose metabolism. AMP-activated protein kinase

SUBMITTER: Koyama D 

PROVIDER: S-EPMC7780059 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature