BCR-ABL1 mutations in patients with imatinib-resistant Philadelphia chromosome-positive leukemia by use of the PCR-Invader assay.
BCR-ABL1 kinase domain mutations were evaluated in 60 imatinib-resistant patients with Philadelphia-positive (Ph(+)) leukemia using PCR-Invader assay and direct sequencing. In chronic myelogenous leukemia (CML)--chronic phase (CP), 5 had P-loop mutations and 3 had T315I mutations. CML-CP patients with high Sokal score showed significantly higher incidence of mutations. P-loop mutations were associated with higher risk of disease progression. In CML-advanced phase, P-loop mutations and T315I mutation were associated with significantly shorter survival. In Ph(+) acute lymphoblastic leukemia, overall survival was poor irrespective of mutational status. The PCR-Invader assay is useful for screening of mutations and prediction of prognosis.
Cancer Education and Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. takaono@hama-med.ac.jp
Takaaki
T
Ono
Shuichi
S
Miyawaki
Fumihiko
F
Kimura
Heiwa
H
Kanamori
Shigeki
S
Ohtake
Kunio
K
Kitamura
Hiroyuki
H
Fujita
Isamu
I
Sugiura
Kensuke
K
Usuki
Nobuhiko
N
Emi
Shigehisa
S
Tamaki
Yasutaka
Y
Aoyama
Hiroyasu
H
Kaya
Tomoki
T
Naoe
Kenichi
K
Tadokoro
Toshikazu
T
Yamaguchi
Ryuzo
R
Ohno
Kazunori
K
Ohnishi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D004252:DNA Mutational Analysis / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D017434:Protein Structure, Tertiary / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D016019:Survival Analysis; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D010770:Phosphotransferases; D016044:Fusion Proteins, bcr-abl