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Chronic Myeloid Leukaemia

  1. Tariq I Mughal1,
  2. John M Goldman2

Published Online: 15 FEB 2013

DOI: 10.1002/9780470015902.a0002181.pub2

eLS

eLS

How to Cite

Mughal, T. I. and Goldman, J. M. 2013. Chronic Myeloid Leukaemia. eLS. .

Author Information

  1. 1

    Tufts University School of Medicine, Boston, Massachusetts, USA

  2. 2

    Imperial College London, London, UK

Publication History

  1. Published Online: 15 FEB 2013

Abstract

Chronic myeloid leukaemia (CML) is a clonal BCR–ABL1-positive myeloproliferative disorder that results from an acquired genetic change in a single pluripotential haematopoietic stem cell. Although CML is rare, the lessons learned from unravelling its molecular biology over the past three decades have resulted in successful treatment for patients and also in a major paradigm shift in cancer medicine in general. Today many forms of cancer are being treated with drugs that target various molecular abnormalities known to play a role in the pathogenesis of the candidate disease. For CML patients, the introduction of the original tyrosine kinase inhibitor (TKI), imatinib mesylate, in 1998 was an important therapeutic milestone with most patients achieving a complete cytogenetic response and prolongation of survival compared with the previous therapies other than allogeneic stem cell transplantation (allo-SCT). A small minority of patients were also able to achieve a complete molecular remission (CMR). With the more recent introduction of the second generation TKIs, dasatinib and nilotinib, the treatment results for the newly diagnosed patient in chronic phase (CP) seem even better, in particular the number of patients achieving CMR. Allo-SCT is increasingly being offered when patients fail at least two lines of TKIs, except for children, where some specialists feel, it is appropriate to offer SCT as first or second line therapy. Efforts are also made to assess the potential for immunotherapy and other novel drugs, such as ponatinib, targeting specific subgroups of patients, for example, those with a mutant T315I clone have been developed.

Key Concepts:

  • Concept of targeted therapy in cancer medicine.

  • Molecular pathogenesis of CML in CP: a single pathogenetic abnormality.

  • Imatinib as a paradigm for successful molecularly targeted therapy.

  • Second and third generation tyrosine kinase inhibitors: successes and challenges.

  • Role of allogeneic stem transplantation in the era of the second generation TKI.

Keywords:

  • chronic myeloid leukaemia;
  • Philadelphia chromosome;
  • BCRABL1 gene;
  • tyrosine kinase inhibitors;
  • imatinib;
  • dasatinib;
  • nilotinib;
  • bosutinib;
  • allogeneic stem cell transplant;
  • kinase domain mutations;
  • mutant T315 clone;
  • ponatinib