Cancer Institute A national cancer institute
designated cancer center

James L. Zehnder, M.D.

Publication Details

  • Laboratory Practice Guidelines for Detecting and Reporting BCR-ABL Drug Resistance Mutations in Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia A Report of the Association for Molecular Pathology JOURNAL OF MOLECULAR DIAGNOSTICS Jones, D., Kamel-Reid, S., Bahler, D., Dong, H., Elenitoba-Johnson, K., Press, R., Quigley, N., Rothberg, P., Sabath, D., Viswanatha, D., Weck, K., Zehnder, J. 2009; 11 (1): 4-11

    Abstract:

    The BCR-ABL tyrosine kinase produced by the t(9;22)(q34;q11) translocation, also known as the Philadelphia chromosome, is the initiating event in chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Targeting of BCR-ABL with tyrosine kinase inhibitors (TKIs) has resulted in rapid clinical responses in the vast majority of patients with CML and Philadelphia chromosome+ ALL. However, long-term use of TKIs occasionally results in emergence of therapy resistance, in part through the selection of clones with mutations in the BCR-ABL kinase domain. We present here an overview of the current practice in monitoring for such mutations, including the methods used, the clinical and laboratory criteria for triggering mutational analysis, and the guidelines for reporting BCR-ABL mutations. We also present a proposal for a public database for correlating mutational status with in vitro and in vivo responses to different TKIs to aid in the interpretation of mutation studies.

    View details for DOI 10.2353/jmoldx.2009.080095

    View details for Web of Science ID 000262419500002

    View details for PubMedID 19095773

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