Fluorescence in situ hybridization (FISH) on peripheral blood smears for monitoring Philadelphia chromosome-positive chronic myeloid leukemia (CML) during interferon treatment: A new strategy for remission assessment

1998 ◽  
Vol 21 (2) ◽  
pp. 90-100 ◽  
Author(s):  
Josef Mühlmann ◽  
Josef Thaler ◽  
Wolfgang Hilbe ◽  
Oliver Bechter ◽  
Martin Erdel ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Interferon Treatment ◽  
Blood Smears ◽  
New Strategy ◽  
Peripheral Blood Smears

A Novel t(9;22;11) Translocation Variant Involving 11q23 in a Patient with Chronic Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Lin Yuehui ◽  
Qinglong Zheng ◽  
Tong Wu ◽  
DAN LIU
Keyword(s):  
Flow Cytometry ◽  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Flow Cytometry Analysis

Background:The progression of Philadelphia chromosome positive chronic myeloid leukemia (CML) is frequently accompanied by cytogenetic evolution, commonly unbalanced chromosomal changes. but balanced chromosomal translocations are very rare in CML, especially translocations involving the 11q23. The few reported cases with blast phase (BP) of CML carrying a 11q23 rearrangement results in insufficient responses to tyrosine kinase inhibitors (TKIs) and possess a poor prognosis. Methods:Cytogenetic analysis , fluorescence in situ hybridization (FISH), RNA sequencing (RNA-seq), targeted genomic sequencing and multi-parametric flow cytometry analysis were performed to identify the chromosome translocations and pathogenic gene alterations in a 36-year-old female with myeloid BP of CML. Results: In BP, the bone marrow (BM) aspiration showed 61% myeloid blasts; Multi-parametric flow cytometry analysis revealed the abnormal myeloid blasts expression of the following antigens: CD117, CD13, CD33, CD38, partially expressed CD15, CD64. Chromosome analysis revealed a t(11;22)(q23;q11) translocation in addition to the t(9;22)(q34;q11). Fluorescence in situ hybridization (FISH) test confirmed that the t(11;22)(q23;q11) involved the mixed lineage leukemia(MLL) gene on 11q23 and RNA sequence revealed MLL-SEPT5 and BCR/ABL1(p210) fusion transcripts positive. Mutations on 339 commonly mutated genes in hematologic malignancies were analyzed by targeted next-generation sequencing showed ASXL1 p.G949Vfs*2 mutation. The patient failed to respond to both imatinib and dasatinib despite the absence of resistance-associated mutations in the BCR/ABL1 gene and she had a myeloid blast crisis at 19 months after initiation of first- and second-generation TKI treatment. After BP, she received ponatinb, a third-generation TKI with chemotherapy. Regretly she didn't achieve a complete remission(CR) and was in the process of salvage transplantation at present. Conclusions:The presence of 11q23 rearrangements in BC of CML is rare and most likely accounts for the adverse clinical outcome. We first report a patient who diagnosed CML with t(11;22)(q23;q11) and MLL-SEPT5 fusion gene positive in BP of CML. The clinical course was aggressive, and therapy was poorly tolerated. Disclosures No relevant conflicts of interest to declare.

Highly Sensitive Fluorescence In Situ Hybridization Method to Detect Double BCR/ABL Fusion and Monitor Response to Therapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3357-3365 ◽  
Author(s):  
Gordon W. Dewald ◽  
William A. Wyatt ◽  
Amy L. Juneau ◽  
Richard O. Carlson ◽  
Alan R. Zinsmeister ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Ph Chromosome ◽  
Cytogenetic Remission

Abstract We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

scholarly journals Fluorescent in-situ hybridization (FISH) for BCR/ABL in chronic myeloid leukemia after bone marrow transplantation

2001 ◽  
Vol 119 (1) ◽  
pp. 16-18
Author(s):  
Maria de Lourdes Lopes Ferrari Chauffaille ◽  
José Salvador Rodrigues Oliveira ◽  
Maura Romeo ◽  
José Kerbauy
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Bone Marrow Transplantation ◽  
Chronic Myeloid Leukemia ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Residual Disease ◽  
Philadelphia Chromosome

CONTEXT: Identification of Philadelphia chromosome or BCR/ABL gene rearrangement in chronic myeloid leukemia is important at diagnosis as well as after treatment. OBJECTIVE: To compare the results of karyotyping using fluorescent in-situ hybridization (FISH) upon diagnosis and 1 year after bone marrow transplantation in 12 patients. TYPE OF STUDY: Diagnostic test and residual disease detection. SETTING: Hematology and Hemotherapy Department, Federal University of São Paulo/Escola Paulista de Medicina, São Paulo, Brazil. SAMPLE: 12 patients with chronic myeloid leukemia at diagnosis and 1 year after bone marrow transplantation. DIAGNOSTIC TEST: Karyotyping was done in the usual way and the BCR/ABL gene-specific probe was used for FISH. MAIN MEASUREMENTS: Disease at diagnosis and residual. RESULTS: At diagnosis, 10 patients presented t(9;22)(q34.1;q11) as well as positive FISH. Two cases did not have metaphases but FISH was positive. After bone marrow transplantation, 8 patients presented normal karyotype, 1 had persistence of identifiable Philadelphia chromosome and 3 had no metaphases. Two cases showed complete chimera and 2 had donor and host cells simultaneously. FISH was possible in all cases after bone marrow transplantation and confirmed the persistence of identifiable Philadelphia chromosome clone in one patient, and identified another that did not present metaphases for analysis. Cases that showed mixed chimera in karyotype were negative for BCR/ABL by FISH. CONCLUSION: The applicability of FISH is clear, particularly for residual disease detection. Classical and molecular cytogenetics are complementary methods.

scholarly journals Highly Sensitive Fluorescence In Situ Hybridization Method to Detect Double BCR/ABL Fusion and Monitor Response to Therapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3357-3365 ◽  
Author(s):  
Gordon W. Dewald ◽  
William A. Wyatt ◽  
Amy L. Juneau ◽  
Richard O. Carlson ◽  
Alan R. Zinsmeister ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Ph Chromosome ◽  
Cytogenetic Remission

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

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