A thirty-five nucleotides BCR-ABL1 insertion mutation of controversial significance confers resistance to imatinib in a patient with chronic myeloid leukemia (CML).
Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients does not achieve the optimal response or are resistant to TKI. ABL1 kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Although deletion or insertion of nucleotides in BCR-ABL1 has rarely been described, we identified a CML patient with an already described 35 nucleotides insertion (BCR-ABL1(35INS)) of controversial significance, that confers resistance to imatinib but sensitivity to dasatinib.
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain. Electronic address: smarce@iconcologia.net.
Silvia
S
Marcé
Hospital General de Granollers, Granollers, Spain.
Montserrat
M
Cortés
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain.
Lurdes
L
Zamora
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain.
Marta
M
Cabezón
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain.
Javier
J
Grau
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain.
Fuensanta
F
Millá
ICO Badalona-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, UAB, Badalona, Spain.
Evarist
E
Feliu
D000328:Adult; D001483:Base Sequence; D001549:Benzamides / Q000627:therapeutic use*; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009711:Nucleotides / Q000737:chemistry*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013844:Thiazoles / Q000627:therapeutic use
C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D009711:Nucleotides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib
BCR-ABL1; CML; Insertion; Mutation; Resistance; TKI