scholarly journals 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

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhanglin Zhang ◽  
Zhiwei Chen ◽  
Mei Jiang ◽  
Shuyuan Liu ◽  
Yang Guo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Effective Means ◽  
Chronic Phase ◽  
Prognostic Impact ◽  
Durable Response

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.

A fluorescence in situ hybridization study of TEL-AML1 fusion gene in B-cell acute lymphoblastic leukemia (1984–2001)

2003 ◽  
Vol 144 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Nathalie Douet-Guilbert ◽  
Frédéric Morel ◽  
Marie-Josée Le Bris ◽  
Angèle Herry ◽  
Geneviève Le Calvez ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Hybridization Study ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals ETV6-RUNX1Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Abir Gmidène ◽  
Hatem Elghezal ◽  
Hlima Sennana ◽  
Yosra Ben Youssef ◽  
Balkiss Meddeb ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Genetic Changes ◽  
Multiple Copies ◽  
B Lineage

In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL), and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH) for the t(12;21). This translocation leadsETV6-RUNX1(previouslyTEL-AML1) fusion gene. 16 patients (28%) hadETV6-RUNX1rearrangement. In addition to this rearrangement, two cases showed a loss of the normalETV6allele, and three others showed an extra signal of theRUNX1gene. Seven patients withoutETV6-RUNX1rearrangement showed extra signals of theRUNX1gene. One out of the 7 patients was also associated with a t(3;12) identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21) among childhood B-lineage ALL and in which we have found multiple copies ofRUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL withETV6-RUNX1gene fusion which is envisaged to play a pivotal role in disease progression.

scholarly journals A New Subtype of Pre-B Acute Lymphoblastic Leukemia With t(5; 12)(q31q33; p12), Molecularly and Cytogenetically Distinct From t(5; 12) in Chronic Myelomonocytic Leukemia

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1716-1722 ◽  
Author(s):  
Iwona Wlodarska ◽  
Anna Aventı́n ◽  
Júlia Inglés-Esteve ◽  
Daniela Falzetti ◽  
Arnold Criel ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lines ◽  
Chromosomal Abnormality ◽  
Gene Fusion ◽  
Lymphoblastic Leukemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia

Abstract Translocation t(5; 12)(q33; p13), resulting in an ETV6/PDGFRB gene fusion, is a recurrent chromosomal abnormality associated with chronic myelomonocytic leukemia (CMML). An analogous translocation was also found in four cell lines with features of pre-B acute lymphoblastic leukemia (ALL). Using fluorescence in situ hybridization (FISH) we show here that in three of these cell lines identical complex rearrangements occurred. However, the regions involved on 5q and 12p are different from the breakpoints in CMML, and the translocation is accompanied by seemingly identical cryptic deletions of both 5q and 12p chromosome sequences in all analyzed pre-B ALL cell lines. The similar cytogenetic, FISH, and immunophenotyping findings in the three cell lines suggest that the t(5; 12)(q31q33; p12) defines a new entity of pre-B ALL.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Separated into Two Subgroups Associated with Survival by BCR-ABL Fluorescence in situ Hybridization of Segmented Cell Nuclei: Report from a Single Institution

2016 ◽  
Vol 136 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Yoshimasa Kamoda ◽  
Kiyotaka Izumi ◽  
Futoshi Iioka ◽  
Takashi Akasaka ◽  
Fumihiko Nakamura ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Nuclei ◽  
Fish Group ◽  
Segmented Cell ◽  
Philadelphia Chromosome Positive

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-. Seg-FISH+ cases were characterized by a higher rate of p210-type BCR-ABL transcripts, higher white cell and blast counts, and a higher rate of myeloid and T-lymphoid antigen expression than Seg-FISH- cases, in addition to ‘major route' cytogenetic abnormalities associated with CML-BC. Eighteen patients were treated with tyrosine kinase inhibitors (TKIs) either alone or in combination with multiagent chemotherapy, and 7 underwent allogeneic hematopoietic stem cell transplantation. Progression-free and overall survivals were greater in the Seg-FISH+ group than in the Seg-FISH- group. These results suggest that the Seg-FISH+ group represents lymphoid CML-BC that occurs de novo, while the Seg-FISH- represents Ph+ ALL in the strict sense, and the two groups are associated with survival when treated with TKIs or TKI-combined therapy.

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