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

Cancer Genet Cytogenet. 2008 May;183(1):77-81. doi: 10.1016/j.cancergencyto.2008.01.024.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzamides
  • Chromosomes, Human, Pair 1*
  • Chromosomes, Human, Pair 17*
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Fusion Proteins, bcr-abl
  • Gene Deletion
  • Genes, abl
  • Genes, p53*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Mutation
  • Piperazines / therapeutic use*
  • Protein Structure, Tertiary / genetics
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics*
  • Pyrimidines / therapeutic use*
  • Translocation, Genetic*

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl