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Cancer Invest. 2015;33(9):451-8. doi: 10.3109/07357907.2015.1065499. Epub 2015 Aug 17.

BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.

Author information

1
a 1 Hemocentro-UNICAMP , University of Campinas, Campinas , São Paulo, Brazil.
2
b 2 Laboratório de Biologia Tumoral , University of São Paulo, São Paulo , São Paulo, Brazil.
3
c 3 Hemorio, Rio de Janeiro , Rio de Janeiro, Brazil.
4
d 4 Instituto Nacional do Câncer, Rio de Janeiro , Rio de Janeiro, Brazil.
5
e 5 Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina de Buenos Aires , Buenos Aires, Argentina.
6
f 6 Hospital das Clínicas de Porto Alegre, Porto Alegre , Rio Grande do Sul, Brazil.
7
g 7 Federal University of Rio de Janeiro , Rio de Janeiro , Rio de Janeiro, Brazil.
8
h 8 Universidade Federal do Paraná , Curitiba, Paraná, Brazil.
9
i 9 Santa Casa de São Paulo, São Paulo , São Paulo, Brazil.
10
j 10 Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais, Brazil.
11
k 11 Hospital Santa Marcelina , São Paulo, São Paulo, Brazil.
12
l 12 Hospital Ramos Mejía , Buenos Aires, Argentina.
13
m 13 Banco Municipal de Sangre del DC , Caracas, Venezuela.
14
n 14 FUNDALEU , Buenos Aires, Argentina.
15
o 15 INCAN , Mexico, D.F., Mexico.
16
p 16 Centro Médico Nacional Siglo XXI , Mexico, D.F., Mexico.
17
q 17 University of São Paulo , Ribeirão Preto, São Paulo, Brazil.
18
r 18 Hospital Israelita Albert Einstein , São Paulo, São Paulo, Brazil.
19
s 19 Hospital Maciel , Montevideo, Uruguay.
20
t 20 Instituto Oncologico Nacional , Panamá, Panama.
21
u 21 MD Anderson Cancer Center , Houston, Texas, USA.

Abstract

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

KEYWORDS:

BCR-ABL mutations; Chronic myeloid leukemia; Imatinib; Resistance; Tyrosine kinase inhibitors

PMID:
26288116
DOI:
10.3109/07357907.2015.1065499
[Indexed for MEDLINE]

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