PMID- 33306831
OWN - NLM
STAT- MEDLINE
DCOM- 20210105
LR  - 20210105
IS  - 1003-9406 (Print)
IS  - 1003-9406 (Linking)
VI  - 37
IP  - 12
DP  - 2020 Dec 10
TI  - [Evolvement of a five-way translocation t(5;9;22;6;17) from a four-way 
      Philadelphia translocation t(5;9;22;6) in a rare case of chronic myeloid 
      leukemia].
PG  - 1395-1398
LID - 10.3760/cma.j.cn511374-20191220-00650 [doi]
AB  - OBJECTIVE: To trace a rare case of chronic myeloid leukemia (CML) with a four-way 
      Philadelphia chromosome variant by cytogenetic analysis in order to provide a 
      basis for the selection of treatment. METHODS: Bone marrow morphology, 
      chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time 
      quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. 
      Point mutations in the tyrosine kinase domain of ABL1 gene were detected by 
      Sanger sequencing. RESULTS: The patient was initially diagnosed as CML in chronic 
      phase (CML-CP) with a chromosomal karyotype of 
      46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant 
      Philadelphia chromosome translocation. Clonal evolution has occurred after 38 
      months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis 
      revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and 
      t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the 
      t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with 
      additional abnormalities were detected in addition to t(5;9;22;6;17). Three 
      mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in 
      the tyrosine kinase domain of the ABL1 gene during the course of disease. The 
      patient did not attain cytogenetic and molecular response to TKIs. CONCLUSION: 
      The four-way variant translocation may be genetically unstable. Clonal evolution 
      and genetic mutations are likely to occur during TKIs treatment, resulting in 
      poor response to drug therapy. This observation, however, needs to be confirmed 
      by large-scale studies.
FAU - Kong, Shu
AU  - Kong S
AD  - Peking University Institute of Hematology, Beijing Key Laboratory of 
      Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Beijing 100044, China. laiyueyun1008@sina.com.
FAU - Gu, Yuqing
AU  - Gu Y
FAU - Qin, Yazhen
AU  - Qin Y
FAU - Wang, Zheng
AU  - Wang Z
FAU - Feng, Lin
AU  - Feng L
FAU - Jiang, Qian
AU  - Jiang Q
FAU - Lai, Yueyun
AU  - Lai Y
LA  - chi
PT  - Case Reports
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Yi Chuan Xue Za Zhi
JT  - Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese 
      journal of medical genetics
JID - 9425197
RN  - 0 (Enzyme Inhibitors)
SB  - IM
MH  - Enzyme Inhibitors/therapeutic use
MH  - Evolution, Molecular
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics
MH  - Mutation/genetics
MH  - *Philadelphia Chromosome
MH  - *Translocation, Genetic
EDAT- 2020/12/12 06:00
MHDA- 2021/01/06 06:00
CRDT- 2020/12/11 17:09
PHST- 2020/12/11 17:09 [entrez]
PHST- 2020/12/12 06:00 [pubmed]
PHST- 2021/01/06 06:00 [medline]
AID - 940637259 [pii]
AID - 10.3760/cma.j.cn511374-20191220-00650 [doi]
PST - ppublish
SO  - Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Dec 10;37(12):1395-1398. doi: 
      10.3760/cma.j.cn511374-20191220-00650.