TY - JOUR
T1 - In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib
AU - Khorashad, Jamshid S.
AU - Milojkovic, Dragana
AU - Mehta, Puja
AU - Anand, Mona
AU - Ghorashian, Sara
AU - Reid, Alistair G.
AU - De Melo, Valeria
AU - Babb, Anna
AU - De Lavallade, Hugues
AU - Olavarria, Eduardo
AU - Marin, David
AU - Goldman, John M.
AU - Apperley, Jane F.
AU - Kaeda, Jaspal S.
PY - 2008/2/15
Y1 - 2008/2/15
N2 - We sought kinase domain (KD) mutations at the start of treatment with dasatinib in 46 chronic myeloid leukemia (CML) patients resistant to or intolerant of imatinib. We identified BCR-ABL mutant subclones in 12 (26%) cases and used pyrosequencing to estimate subsequent changes in their relative size after starting dasatinib. Four patients lost their mutations, which remained undetectable, 3 patients retained the original mutation or lost it only transiently, 3 lost their original mutations but acquired a new mutation (F317L), and 2 developed another mutation (T315I) in addition to the original mutation within the same subclone. This study shows that expansion of a mutant Ph-positive clone that responds initially to a second generation tyrosine kinase inhibitor may be due either to late acquisition of a second mutation in the originally mutated clone, such as the T315I, or to acquisition of a completely new mutant clone, such as F317L.
AB - We sought kinase domain (KD) mutations at the start of treatment with dasatinib in 46 chronic myeloid leukemia (CML) patients resistant to or intolerant of imatinib. We identified BCR-ABL mutant subclones in 12 (26%) cases and used pyrosequencing to estimate subsequent changes in their relative size after starting dasatinib. Four patients lost their mutations, which remained undetectable, 3 patients retained the original mutation or lost it only transiently, 3 lost their original mutations but acquired a new mutation (F317L), and 2 developed another mutation (T315I) in addition to the original mutation within the same subclone. This study shows that expansion of a mutant Ph-positive clone that responds initially to a second generation tyrosine kinase inhibitor may be due either to late acquisition of a second mutation in the originally mutated clone, such as the T315I, or to acquisition of a completely new mutant clone, such as F317L.
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U2 - 10.1182/blood-2007-06-096396
DO - 10.1182/blood-2007-06-096396
M3 - Article
C2 - 17982022
AN - SCOPUS:41349085814
SN - 0006-4971
VL - 111
SP - 2378
EP - 2381
JO - Blood
JF - Blood
IS - 4
ER -