Open AccessRapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays
Author(s) -
Yin C. Cameron,
Cortes Jorge,
Galbincea John,
Reddy Neelima,
Breeden Megan,
Jabbour Elias,
Luthra Rajyalakshmi,
Jones Dan
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01627.x
Subject(s) - chronic myelogenous leukemia , imatinib mesylate , tyrosine kinase inhibitor , imatinib , point mutation , mutation , tyrosine kinase , cancer research , mutation testing , biology , pyrosequencing , abl , microbiology and biotechnology , leukemia , genetics , gene , myeloid leukemia , cancer , signal transduction
Treatment of CML with the tyrosine kinase inhibitor (TKI) imatinib mesylate results in the emergence of point mutations within the kinase domain (KD) of the BCR‐ABL1 fusion transcript. The introduction of next‐generation TKIs that can overcome the effects of some BCR‐ABL1 KD mutations requires quantitative mutation profiling methods to assess responses. We report the design and validation of such quantitative assays, using pyrosequencing and mutation‐specific RT‐PCR techniques, to allow sequential monitoring and illustrate their use in tracking specific KD mutations (e.g. G250E, T315I, and M351T) following changes in therapy. Pyrosequencing and mutation‐specific RT‐PCR allows sequential monitoring of specific mutations and identification of rapid clonal shifts in response to kinase inhibitor therapy in CML. Rapid reselection of TKI‐resistant clones occurs following therapy switch in CML. ( Cancer Sci 2010)