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BMC Cancer. 2019 Oct 8;19(1):935. doi: 10.1186/s12885-019-6137-8.

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.

Zhang Z1,2, Chen Z2,3, Jiang M1, Liu S1, Guo Y1, Wan L1, Li F4,5,6.

Author information

1
Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
2
Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, Nanchang, 330006, China.
3
Department of Hematology, the First Affiliated Hospital of Nanchang University, No. 17 Yongwai Street, Donghu District, Nanchang, 330006, Jiangxi, China.
4
Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, Nanchang, 330006, China. yx021021@sina.com.
5
Department of Hematology, the First Affiliated Hospital of Nanchang University, No. 17 Yongwai Street, Donghu District, Nanchang, 330006, Jiangxi, China. yx021021@sina.com.
6
Jiangxi Key Laboratory of Molecular Diagnosis and Precision Medicine, Nanchang, 330006, China. yx021021@sina.com.

Abstract

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.

KEYWORDS:

BCR-ABL1; Clonal evolution; Fluorescence in situ hybridization; Prognosis

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