New Insights Into Biology of Chronic Myeloid Leukemia: Implications in Therapy

Curr Cancer Drug Targets. 2013 Sep;13(7):711-23. doi: 10.2174/15680096113139990085.

Abstract

Over the past decades the prognosis of patients with Chronic Myeloid Leukemia (CML) has radically changed due to groundbreaking scientific and translational studies that have revealed the biologic basis of such a hematologic malignancy. These studies have led to the rapid development of many BCR-ABL specific tyrosine kinase inhibitors (TKIs), such as Imatinib, Nilotinib and Dasatinib, which have improved 10-years survival to more than 80%. Although these therapies represent a landmark step in the race for the cure of CML, they did not change the progression in advanced phase of disease. Therefore unravel the molecular mechanisms and the biological basis of CML, especially during the advanced stage, is of seminal importance as this would result in the design of more effective and less toxic therapies. In such a scenario, several novel drugs designed to specifically target biological features of CML cells are currently in clinical trials with promising results that would provide not only improve the therapeutic armamentarium but also to overcome drug resistance of this tumor. Here we review recent advances in biology of CML and their therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Drug Design*
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Molecular Targeted Therapy*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / enzymology
  • Neoplastic Stem Cells / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl