Vol 1, No 3 (2010)
Review paper
Published online: 2010-07-27

open access

Page views 972
Article views/downloads 12217
Get Citation

Connect on Social Media

Connect on Social Media

Pathogenesis of chronic myeloid leukemia - from gene to targeted therapy

Joanna Żołnierowicz, Jerzy Kawiak, Grażyna Hoser
Hematologia 2010;1(3):195-218.

Abstract

The occurrence of chronic myeloid leukemia (CML) is related to the appearance of reciprocal chromosomal translocation (9;22)(q34;q11). As a result of translocation between chromosomes 9 and 22, shortened chromosome 22 - Philadelphia (Ph) chromosome arises, coding for constitutively active protein tyrosine kinase, BCR-ABL1. The subsequent deregulation of the ABL1 kinase activity in cells leads to enhanced proliferation, resistance to apoptosis and altered adhesion. The discovery of imatinib, a relatively specific tyrosine kinase inhibitor, including ABL1 and BCR-ABL1 kinases, was a breakthrough in CML treatment. Imatinib functions by binding to the active site of ABL1 kinase in an inactive conformation, thus blocking the ATP binding site crucial for enzyme activity. Although imatinib has revolutionized CML therapy, appearance of resistance to this inhibitor leads to CML progression. In case of imatinib-resistance, several possible strategies exist for the management of the disease, which include increasing the dose of imatinib, changing therapy to the 2nd generation tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation. CML therapy, appearance of resistance to this inhibitor leads to CML progression. In case of imatinib-resistance, several possible strategies exist for the management of the disease, which include increasing the dose of imatinib, changing therapy to the 2nd generation tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation.CML therapy, appearance of resistance to this inhibitor leads to CML progression. In case of imatinib-resistance, several possible strategies exist for the management of the disease, which include increasing the dose of imatinib, changing therapy to the 2nd generation tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation.
Hematologia 2010; 1, 3: 195-218

Article available in PDF format

View PDF (Polish) Download PDF file



Hematology in Clinical Practice