TY - JOUR
T1 - Characteristics and outcome of chronic myeloid leukemia patients with E255K/V BCR–ABL kinase domain mutations
AU - Naqvi, Kiran
AU - Cortes, Jorge E.
AU - Luthra, Raja
AU - O’Brien, Susan
AU - Wierda, William
AU - Borthakur, Gautam
AU - Kadia, Tapan
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Rios, Mary Beth
AU - Dellasala, Sara
AU - Pierce, Sherry
AU - Jabbour, Elias
AU - Patel, Keyur
AU - Kantarjian, Hagop
N1 - Funding Information:
Acknowledgements Dr. Cortes has received research support from Ariad, BMS, Novartis, Pfizer, and Teva. Dr. Cortes is consultant for Ariad, Novartis, BMS, and Pfizer.
Publisher Copyright:
© 2018, The Japanese Society of Hematology.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Kinase domain (KD) mutations of ABL1 represent the most common resistance mechanism to tyrosine kinase inhibitors (TKI) in CML. Besides T315I, mutations in codon 255 are highly resistant mutations in vitro to all TKI. We aimed to study the incidence, prognosis, and response to treatment in patients with E255K/V. We evaluated 976 patients by sequencing of BCR–ABL1 fusion transcript for ABL1 KD mutations. We identified KD mutations in 381 (39%) patients, including E255K/V in 48 (13% of all mutations). At mutation detection, 14 patients (29%) were in chronic phase (CP), 12 (25%) in accelerated phase (AP), and 22 (46%) in blast phase (BP). 9/14 CP patients responded to treatment (best response complete hematologic response—CHR-4; complete cytogenetic response—CCyR-1; major molecular response—MMR-4); only 4/12 AP patients (CHR 3; MMR 1) and 7/22 BP patients responded (CCyR 2; MMR 2; partial cytogenetic response—PCyR-3). After a median follow-up of 65 months from mutation detection, 36 patients (75%) died: 9/14 (64%) in CP, 9/12 (75%) in AP, and 18/22 (82%) in BP (p = 0.003); median overall survival was 12 months. Patients with E255K/V mutation have a poor prognosis, regardless of the stage of the disease at detection.
AB - Kinase domain (KD) mutations of ABL1 represent the most common resistance mechanism to tyrosine kinase inhibitors (TKI) in CML. Besides T315I, mutations in codon 255 are highly resistant mutations in vitro to all TKI. We aimed to study the incidence, prognosis, and response to treatment in patients with E255K/V. We evaluated 976 patients by sequencing of BCR–ABL1 fusion transcript for ABL1 KD mutations. We identified KD mutations in 381 (39%) patients, including E255K/V in 48 (13% of all mutations). At mutation detection, 14 patients (29%) were in chronic phase (CP), 12 (25%) in accelerated phase (AP), and 22 (46%) in blast phase (BP). 9/14 CP patients responded to treatment (best response complete hematologic response—CHR-4; complete cytogenetic response—CCyR-1; major molecular response—MMR-4); only 4/12 AP patients (CHR 3; MMR 1) and 7/22 BP patients responded (CCyR 2; MMR 2; partial cytogenetic response—PCyR-3). After a median follow-up of 65 months from mutation detection, 36 patients (75%) died: 9/14 (64%) in CP, 9/12 (75%) in AP, and 18/22 (82%) in BP (p = 0.003); median overall survival was 12 months. Patients with E255K/V mutation have a poor prognosis, regardless of the stage of the disease at detection.
KW - Chronic myeloid leukemia
KW - Mutation
KW - Resistance
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U2 - 10.1007/s12185-018-2422-6
DO - 10.1007/s12185-018-2422-6
M3 - Article
C2 - 29464484
AN - SCOPUS:85042231597
SN - 0925-5710
VL - 107
SP - 689
EP - 695
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 6
ER -