Laboratory Practice Guidelines for Detecting and Reporting BCR-ABL Drug Resistance Mutations in Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia

• DOI: 10.2353/jmoldx.2009.080095
• Publication Date: 2008-12-19T01:54:30Z
• Authors: Dan Jones; Suzanne Kamel-Reid; David Bahler; Henry Dong; Kojo Elenitoba-Jo...; Richard Press; Neil Quigley; Paul Rothberg; Dan Sabath; David Viswanatha; Karen Weck; James Zehnder
• Keywords: 0301 basic medicine; Clinical Trials as Topic; 0303 health sciences; 03 medical and health sciences; Drug Resistance, Neoplasm; Data Collection; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mutation; Fusion Proteins, bcr-abl; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; 3. Good health

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 alsopresent 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.