Figure 3.

Signaling pathways involved in the development of target therapy resistance. (A) Molecular structure of BCR-ABL1 kinase domain with some mutations (indicated in red). (B) Gene amplification can lead to overproduction of tyrosine kinase. (C) Constitutive activation of signaling pathways, such as PI3K-AKT, RAS-MAPK, and JAK-STAT, result in cell proliferation and anti-apoptotic mechanisms. (D) Intracellular concentrations of TKIs can be modified through membrane transporters that may cause increased efflux or decreased influx. (E) The most common chromosome abnormalities involved in karyotype evolution are trisomy 8, trisomy 19, trisomy 21, second Ph chromosome, and isochromosome 17.