Imatinib resistance in a novel translocation der(17)t(1;17)(q25;p13) with loss of TP53 but without BCR/ABL kinase domain mutation in chronic myelogenous leukemia.
We describe here two novel translocations, t(7;14)(p22;q13) and der(17)t(1;17)(q25;p13), in a 41-year-old man with an accelerated phase (AP) of chronic myelogenous leukemia (CML). Chromosome analysis initially showed 46,XY,t(7;14)(p13;q22),t(9;22)(q34;q11.2)[20]. In 3 years, the karyotype evolved to 45,X,-Y,der(7)t(7;14)(p13;q22),t(9;22)(q34;q11.2),-14,der(17)t(1;17)(q25;p13),+der(22)t(9;22)[20], accompanied with a resistance to imatinib mesylate. The TP53 was deleted from the der(17)t(1;17)(q25;p13), but there was no mutation of TP53 in the remaining allele. Mutations in the BCR/ABL kinase domain could not be detected as well. Morphologically, dysplastic changes including pseudo-Pelger-Huët anomaly appeared in the bone marrow cells. These findings suggest that the t(7;14)(p22;q13) translocation had a crucial role in the progression to CML-AP, and that the resistance to imatinib may be due to the additional cytogenetic abnormalities, including der(17)t(1;17)(q25;p13), but not to BCR/ABL mutations.
Yamamoto
Katsuya
K
Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Yakushijin
Kimikazu
K
Nishikawa
Shinichiro
S
Minagawa
Kentaro
K
Katayama
Yoshio
Y
Shimoyama
Manabu
M
Matsui
Toshimitsu
T
D000328:Adult; D001549:Benzamides; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl; D017353:Gene Deletion; D016313:Genes, abl; D016158:Genes, p53; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D014178:Translocation, Genetic
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl