The different characteristics of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia / 中华血液学杂志
Chinese Journal of Hematology
; (12): 21-25, 2013.
Artículo
en Chino
| WPRIM (Pacífico Occidental)
| ID: wpr-323457
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To identify the distribution and differentiation of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL).</p><p><b>METHODS</b>Bone marrow or peripheral blood samples of 112 imatinib resistant CML patients and 21 Ph(+)ALL patients were obtained from the first affiliated hospital of Soochow university according to local law. Total RNA was extracted from the mononuclear cells using a TRIzol reagent. ABL kinase domain (KD) mutation was detected by direct sequencing.</p><p><b>RESULTS</b>Of the 112 imatinib resistant CML patients, 54.46%(61 cases) had ABL KD mutation. Twenty-three mutants were identified in 20 amino acid sites and 23.21% (26 cases) ABL KD mutations were in P-loop region. ABL KD mutations were also detected in 71.43% (15 cases) imatinib resistant Ph(+)ALL patients, with 10 mutations in 8 amino acid sites. The most frequent mutation was T315I (28.57%), followed by E255K/V (19.05%) and Y253F/H (14.29%). The frequency of T315I was much higher in imatinib resistant Ph(+) ALL than that in imatinib resistant CML (P = 0.001). Ph(+)ALL with additional chromosomal aberrations also had a higher rate of ABL KD mutation than that of CML (P = 0.010). Ph(+)ALL gained ABL KD mutation faster than CML (P < 0.010).</p><p><b>CONCLUSION</b>Chinese imatinib resistant CML and Ph(+)ALL patients had different characteristics in ABL KD mutation. The rate of ABL KD mutation in Ph(+)ALL with additional chromosomal aberrations was much higher than that of CML with additional chromosomal aberrations.</p>
Texto completo:
Disponible
Base de datos:
WPRIM (Pacífico Occidental)
Asunto principal:
Farmacología
/
Piperazinas
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Pirimidinas
/
Benzamidas
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Proteínas Tirosina Quinasas
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Cromosoma Filadelfia
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Leucemia Mielógena Crónica BCR-ABL Positiva
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Proteínas Proto-Oncogénicas c-abl
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Aberraciones Cromosómicas
/
Resistencia a Antineoplásicos
Tipo de estudio:
Estudio pronóstico
Límite:
Adolescente
/
Adulto
/
Anciano
/
Femenino
/
Humanos
Idioma:
Chino
Revista:
Chinese Journal of Hematology
Año:
2013
Tipo del documento:
Artículo