title: [Characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia].
abstract: OBJECTIVE
  To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).
  
  
  METHODS
  The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.
  
  
  RESULTS
  In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.
  
  
  CONCLUSIONS
  T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.
authors.affiliation: Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450008, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yingling
authors.initials: Y
authors.lastname: Zu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Mengjuan
authors.initials: M
authors.lastname: Li
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
mesh_terms: D000208:Acute Disease; D001752:Blast Crisis; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl