title: 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.
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.
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: dajones@mdanderson.org.
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; The University Health Network, Toronto, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; ARUP Laboratories, Salt Lake City, Utah.
authors.forename: David
authors.initials: D
authors.lastname: Bahler
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; Genzyme Genetics, New York City, New York.
authors.forename: Henry
authors.initials: H
authors.lastname: Dong
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Kojo
authors.initials: K
authors.lastname: Elenitoba-Johnson
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; Oregon Health & Science University, Portland, Oregon.
authors.forename: Richard
authors.initials: R
authors.lastname: Press
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; Molecular Pathology Laboratory Network, Inc., Maryville, Tennessee.
authors.forename: Neil
authors.initials: N
authors.lastname: Quigley
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; University of Rochester Medical Center, Rochester, New York.
authors.forename: Paul
authors.initials: P
authors.lastname: Rothberg
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; University of Washington, Seattle, Washington.
authors.forename: Dan
authors.initials: D
authors.lastname: Sabath
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; Mayo Clinic, Rochester, Minnesota.
authors.forename: David
authors.initials: D
authors.lastname: Viswanatha
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Karen
authors.initials: K
authors.lastname: Weck
authors.affiliation: ABL Mutation Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Houston, Texas; Stanford University, Stanford, California.
authors.forename: James
authors.initials: J
authors.lastname: Zehnder
mesh_terms: D002986:Clinical Trials as Topic; D003625:Data Collection / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: D016044:Fusion Proteins, bcr-abl