Published online before print December 18, 2008

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Copyright © 2009 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2009.080095

Accepted for publication October 2, 2008.

Article

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

Dan Jones^*@, Suzanne Kamel-Reid^*, David Bahler^*, Henry Dong^*¶, Kojo Elenitoba-Johnson^*||, Richard Press^***, Neil Quigley^*, Paul Rothberg^*, Dan Sabath^*, David Viswanatha^*¶¶, Karen Weck^*||||, and James Zehnder^****

From the ABL Mutation Working Group* of the Association for Molecular Pathology, Clinical Practice Committee; University of Texas M. D. Anderson Cancer Center, Houston, Texas; The University Health Network, Toronto, Canada; ARUP Laboratories, Salt Lake City, Utah; Genzyme Genetics,^¶ New York City, New York; the University of Michigan Medical School,^|| Ann Arbor, Michigan; Oregon Health & Science University,** Portland, Oregon; the Molecular Pathology Laboratory Network, Inc., Maryville, Tennessee; the University of Rochester Medical Center, Rochester, New York; the University of Washington, Seattle, Washington; the Mayo Clinic,^¶¶ Rochester, Minnesota; the University of North Carolina,^|||| Chapel Hill, North Carolina; and Stanford University,*** Stanford, California

^@ To whom correspondence should be addressed. E-mail: dajones{at}mdanderson.org.

	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.

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