Molecular and Therapeutic Clues in Chronic Myeloid Leukemia
Pp. 3-80 (78)
Gabriella Marfe, Giovanna Mirone, Arvind Shukla and Carla Di Stefano
Chronic myeloid leukemia (CML) originates from pluripotent hematopoietic
stem cells that acquire translocation between the BCR gene on chromosome 22 and the
ABL proto-oncogene on chromosome 9. Such rearrangement leads to the the
Philadelphia (Ph) chromosome and the oncogenic fusion protein formation. This
oncoprotein induces cell proliferation, causes abnormal migration, and reduces
apoptosis. The suppression of BCR-ABL protein with imatinib and other specific
tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment and is currently
regarded as the gold standard of targeted cancer therapy. However, drug resistance to
anti-cancer chemotherapy is a significant barrier to the treatment of leukemia patients.
Many times, resistance results from molecular adaptation to drug exposure, such as
genetic mutation of key enzymes, upregulation of pro-survival compensatory signaling
pathways, and altered drug transport. In this chapter, we reviewed the literature on the
CML molecular biology, molecular targeted agents and their mechanisms of resistance.
Leukemia, resistance, TKIs, BCR-ABL, Philadelphia (Ph)
chromosome, leukemia stem cells (LSCs), imatinib.
Department of Biochemistry and Biophysics, Second University of Naples, via De Crecchio 7, Naples 80138, Italy.