PMID- 31594548
OWN - NLM
STAT- MEDLINE
DCOM- 20200213
LR  - 20200213
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Oct 8
TI  - Heterogeneous BCR-ABL1 signal patterns identified by fluorescence in situ 
      hybridization are associated with leukemic clonal evolution and poorer prognosis 
      in BCR-ABL1 positive leukemia.
PG  - 935
LID - 10.1186/s12885-019-6137-8 [doi]
LID - 935
AB  - BACKGROUND: Although extensive use of tyrosine kinase inhibitors has resulted in 
      high and durable response rate and prolonged survival time in patients with 
      BCR-ABL1 positive chronic myeloid leukemia (CML) and acute leukemia, relapse and 
      drug resistance still remain big challenges for clinicians. Monitoring the 
      expression of BCR-ABL1 fusion gene and identifying ABL kinase mutations are 
      effective means to predict disease relapse and resistance. However, the 
      prognostic impact of BCR-ABL1 signal patterns detected by fluorescence in situ 
      hybridization (FISH) remains largely unaddressed. METHODS: BCR-ABL1 signal 
      patterns were analyzed using FISH in 243 CML-chronic phase (CML-CP), 17 CML-blast 
      phase (CML-BP) and 52 BCR-ABL1 positive acute lymphoblastic leukemia (ALL) 
      patients. RESULTS: The patterns of BCR-ABL1 signals presented complexity and 
      diversity. A total of 12 BCR-ABL1 signals were observed in this cohort, including 
      1R1G2F, 1R1G1F, 2R1G1F, 1R2G1F, 2R2G1F, 1R2G2F, 1R1G3F, 1G3F, 2G3F, 1G4F, 1R1G4F 
      and 1R4F. Complex BCR-ABL1 signal patterns (>/= two types of signal patterns) were 
      observed in 52.9% (n = 9) of the CML-BP patients, followed by 30.8% (n = 16) of 
      the ALL patients and only 2.1% (n = 5) of the CML-CP patients. More importantly, 
      five clonal evolution patterns related to disease progression and relapse were 
      observed, and patients with complex BCR-ABL1 signal patterns had a poorer overall 
      survival (OS) time compared with those with single patterns (5.0 vs.15.0 months, 
      p = 0.006). CONCLUSIONS: Our data showed that complex BCR-ABL1 signal patterns 
      were associated with leukemic clonal evolution and poorer prognosis in BCR-ABL1 
      positive leukemia. Monitoring BCR-ABL1 signal patterns might be an effective 
      means to provide prognostic guidance and treatment choices for these patients.
FAU - Zhang, Zhanglin
AU  - Zhang Z
AD  - Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang 
      University, Nanchang, 330006, China.
AD  - Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, 
      Nanchang, 330006, China.
FAU - Chen, Zhiwei
AU  - Chen Z
AD  - Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, 
      Nanchang, 330006, China.
AD  - Department of Hematology, the First Affiliated Hospital of Nanchang University, 
      No. 17 Yongwai Street, Donghu District, Nanchang, 330006, Jiangxi, China.
FAU - Jiang, Mei
AU  - Jiang M
AD  - Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang 
      University, Nanchang, 330006, China.
FAU - Liu, Shuyuan
AU  - Liu S
AD  - Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang 
      University, Nanchang, 330006, China.
FAU - Guo, Yang
AU  - Guo Y
AD  - Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang 
      University, Nanchang, 330006, China.
FAU - Wan, Lagen
AU  - Wan L
AD  - Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang 
      University, Nanchang, 330006, China.
FAU - Li, Fei
AU  - Li F
AUID- ORCID: 0000-0002-7765-5975
AD  - Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, 
      Nanchang, 330006, China. yx021021@sina.com.
AD  - Department of Hematology, the First Affiliated Hospital of Nanchang University, 
      No. 17 Yongwai Street, Donghu District, Nanchang, 330006, Jiangxi, China. 
      yx021021@sina.com.
AD  - Jiangxi Key Laboratory of Molecular Diagnosis and Precision Medicine, Nanchang, 
      330006, China. yx021021@sina.com.
LA  - eng
GR  - 81760539/the National Natural Science Foundation of China/
GR  - 81560036, 81560034/the National Natural Science Foundation of China/
GR  - 20151BDH80043/Science and Technology Cooperation Program of Jiangxi Province/
PT  - Journal Article
DEP - 20191008
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Clonal Evolution
MH  - Disease Progression
MH  - Female
MH  - Fusion Proteins, bcr-abl/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/mortality/pathology
MH  - Prognosis
MH  - Survival Rate
MH  - Young Adult
PMC - PMC6781398
OTO - NOTNLM
OT  - BCR-ABL1
OT  - Clonal evolution
OT  - Fluorescence in situ hybridization
OT  - Prognosis
COIS- The authors declare that they have no competing interests.
EDAT- 2019/10/09 06:00
MHDA- 2020/02/14 06:00
PMCR- 2019/10/08
CRDT- 2019/10/10 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2019/09/04 00:00 [accepted]
PHST- 2019/10/10 06:00 [entrez]
PHST- 2019/10/09 06:00 [pubmed]
PHST- 2020/02/14 06:00 [medline]
PHST- 2019/10/08 00:00 [pmc-release]
AID - 10.1186/s12885-019-6137-8 [pii]
AID - 6137 [pii]
AID - 10.1186/s12885-019-6137-8 [doi]
PST - epublish
SO  - BMC Cancer. 2019 Oct 8;19(1):935. doi: 10.1186/s12885-019-6137-8.