Chronic Myeloid Leukaemia

Stem cell transplantation for this disease has become less frequent since the use of tyrosine kinase inhibitors (TKIs). The department has taken part in a number of international clinical trials on the use of first and second generation TKIs. Currently patients who are resistant to TKIs are investigated for kinase mutations by D-HPLC and direct sequencing. This information has been useful in the management of these patients in deciding when transplantation might be appropriate.

"BCR-ABL kinase domain mutations in Imatinib Mesylate resistant / intolerant chronic myeloid leukaemia patients" Lisa O' Connor, Stephen Langabeer, Shaun McCann, Eibhlin Conneally American Association for Cancer Research (AACR) presentation given in San Diego, California in April 2008:

Detailed findings from our investigation of the mutational status of chronic myeloid leukaemia patients resistant to Imatinib Mesylate. A range of BCR-ABL kinase domain mutations were identified including mutations in each of the four functional regions of BCR-ABL, the p-loop region (M244V, G250E, Q252H), the IM binding domain (T315I, F317L), the catalytic domain (M351T, E355G) and the activation domain (L387M). The majority of these patients remain in chronic phase disease on treatment with second generation TKIs, Dasatinib & Nilotinib. The T315I mutation is resistant to TKIs and patients with this mutation and require stem cell transplantation.

Dr Lisa O'Connor (Postgraduate Researcher)

Publications

Hayat A, McCann SR, Langabeer S, Irvine S, McMullin MF, Conneally E..
Effective use of imatinib-mesylate in the treatment of relapsed chronic myeloid leukaemia after allogeneic transplantation.
Haematologica. 94(2):296-298. 2009.

LM O'Connor, S Langabeer, SR McCann, E Conneally. Restoration of donor chimerism by nilotinib in a chronic myeloid leukemia leukaemia patient post mutation-associated imatinib resistace and allogeneic stem cell transplant failure.

Principle Investigators

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