Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate.
Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable improvements in the clinical and laboratory features were noted, and the frequency of ABL1-rearranged peripheral blood cells decreased from 56% to 11%. At d 92, an additional t(12;13)(p12;q13), with the 12p breakpoint proximal to ETV6, was found. The patient relapsed into BC 126 d after the start of the imatinib mesylate treatment and succumbed to the disease shortly afterwards. No mutations in the tyrosine kinase domain of ABL1 of the ETV6/ABL1 fusion were identified in the second BC. However, whereas the ETV6/ABL1 expression was seemingly the same at diagnosis and at second BC, the expression of ETV6 was markedly lower at the second BC. This decreased expression of wild-type ETV6 may have been a contributory factor for the relapse.
Barbouti
Aikaterini
A
Department of Clinical Genetics, Lund University Hospital, Sweden. Aikaterini.Barmpouti@klingen.lu.se
Ahlgren
Tomas
T
Johansson
Bertil
B
Höglund
Mattias
M
Lassen
Carin
C
Turesson
Ingemar
I
Mitelman
Felix
F
Fioretos
Thoas
T
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D017809:Fatal Outcome; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D012008:Recurrence; D000097764:ETS Translocation Variant 6 Protein
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011505:Protein-Tyrosine Kinases; D011743:Pyrimidines; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein