title: T315I mutation in Ph-positive acute lymphoblastic leukemia is associated with a highly aggressive disease phenotype: three case reports.
abstract: T315I mutation in BCR-ABL causes resistance to therapy with tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) cases. We report three cases of relapse accompanied by T315I mutation during rapid disease progression. Case 1 was a 64-year-old male. During chemotherapy, qPCR detected a decrease of BCR-ABL to 190 copies once, but this suddenly increased to 22,000 copies. The patient received dasatinib, but the disease relapsed hematologically when the T315I mutation was detected. Retrospective analysis revealed that the T315I mutated clone already existed at the molecular relapse occurrence. Case 2 was a 25-year-old male. The patient underwent bone marrow transplantation (BMT) at the first molecular complete remission (CR), but 102 days after BMT, the ALL relapsed at the molecular level. Although he received imatinib, ALL immediately fully relapsed; the T315I mutation was detected. Case 3 was a 40-year-old female. Molecular CR was achieved by induction therapy, but ALL relapsed at the molecular level (9,200 copies). The patient received dasatinib, but relapsed hematologically, and the T315I mutation was observed. She underwent umbilical cord blood transplantation, but relapsed. In these three cases, survival from the time of the T315I mutation detection was 4, 2, and 6 months, respectively. The T315I mutation in Ph(+) ALL was associated with a highly aggressive disease phenotype. In order to make appropriate therapeutic decisions, it is important to analyze the mutations immediately at the time of molecular relapse.
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Minami
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000328:Adult; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018628:Gene Dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl