Abstract
BackgroundAlthough 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.MethodsBCR-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.ResultsThe 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).ConclusionsOur 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.
Highlights
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
The patterns of BCR-ABL1 signal present complexity and diversity To explore the characteristics of BCR-ABL1 signals among CML-chronic phase (CML-CP), CML-blast phase (CML-BP) and acute lymphoblastic leukemia (ALL) patients, we assessed and analyzed BCR-ABL1 signals in 243 CML-CP, 17 CML-BP and 52 BCR-ABL1 positive ALL patients using Dual color (DCDF)-fluorescence in situ hybridization (FISH)
Complex BCR-ABL1 signal patterns are more frequently detected in CML-BP and ALL patients We further found that only six types of signals were observed in CML-CP patients, while 12 and 10 types of signals were detected in ALL and CML-BP patients, respectively (Table 1)
Summary
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. Extensive use of tyrosine kinase inhibitors (TKIs) has resulted in high and durable response rate as well as prolonged survival time in BCR-ABL1 positive CML or ALL patients, relapse and drug resistance still remain big challenges for clinicians. Monitoring the expression of BCR-ABL1 fusion gene by quantitative PCR (q-PCR) and identifying ABL kinase mutations by sequencing are effective means to predict disease relapse and resistance. The prognostic impact of BCR-ABL1 signal patterns identified by DCDF-FISH in BCR-ABL1 positive leukemia patients remains largely unaddressed
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