Fluorescence in situ hybridization for the BCR-ABL fusion gene in a patient with imatinib mesylate-resistant chronic myelogenous leukaemia in extramedullary blast crisis

2003 ◽  
Vol 121 (4) ◽  
pp. 533-533 ◽  
Author(s):  
Takehiko Mori ◽  
Rie Yamazaki ◽  
Yasuo Ikeda ◽  
Shinichiro Okamoto
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukaemia ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Myelogenous Leukaemia ◽  
Extramedullary Blast Crisis

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

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.

A Phase I/II Dose Escalating Study of Daunorubicin Combined with Imatinib Mesylate and Cytarabine as Induction Therapy for Chronic Myelogenous Leukaemia in Myeloid Blast Crisis. Preliminary Results of the AFR01 Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1002-1002 ◽  
Author(s):  
Philippe Rousselot ◽  
Laurence Legros ◽  
Joelle Guilhot ◽  
Mauricette Michallet ◽  
Francois Xavier Mahon ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Dose Level ◽  
Chronic Myelogenous Leukaemia ◽  
Blast Crisis ◽  
Myelogenous Leukaemia ◽  
Toxic Dose ◽  
Hematologic Response ◽  
Grade 3 ◽  
Level 2 ◽  
Dose Escalating

Abstract The prognosis of patients (pts) with chronic myelogenous leukaemia (CML) in blast crisis (BC) remains poor. Despite better result with imatinib mesylate (IM), overall hematologic response rates with IM alone are about 50% including 13% of pts reaching complete hematologic remission (CHR). Response duration is short and median survival is 6 to 7 months. Daunorubicin and cytarabine are 2 major drugs for acute myeloblastic leukaemia and have additive or synergistic in vitro effects with IM, depending of the cell line studied. We therefore planned a dose escalating study in an attempt to assess the safety and the efficacy of IM associated with chemotherapy. We combined fixed doses of IM (600 mg daily started 3 days before chemotherapy) and cytarabine (100 mg/m² per day as a continuous IV infusion D1 to D7) with increasing dosages of daunorubicin (cohort 1: no daunorubicin, cohorts 2, 3 and 4 : 15, 30 and 45 mg/m²/day D1 to D3 respectively). G-CSF was administered from D9 until haematological recovery. No PK analysis were performed in this study. Unacceptable toxicities were defined as aplasia duration ≥ 45 days and/or unusual grade 3/4 toxicities. Lowest Toxic Dose was defined as the occurence of unacceptable toxicities in ≥2/6 pts per cohort. Maximum Tolerated Dose defined the recommended dose i.e dose level at which 1 or less than 1 unacceptable toxicity occured in 6 pts. Pts aged ≥18 years with CML myeloid BC were eligible if not previously exposed to IM (n=6 pts evaluable for toxicity in each cohort). 20 pts (median age 55 range 29–74) have been enrolled, 19 pts being evaluable (1 pt with lymphoid BC was excluded). Median follow up is 9 months. Grade 3 to 4 non haematological toxicities were hepatitis not related to IM (n=1, dose level 1), spleen pain (n=1, dose level 2), hyperbilirubinemia (n=1, dose level 2) and skin rash (n=1, dose level 3). All responding pts had a neutrophil recovery before D45 (median duration of neutropenia 16 days, range 1–44); one pt in cohort 3 experienced a thrombocytopenia (< 100 G/l) for longer than 45 days leading to recommend the 30 mg/sq dosage of daunorubicin for the further pts included in the study. CHR was achieved in 45% (n=9) of cases, including 5 pts in complete cytogenetic response(CCR). Median CHR duration was 5 months (range 0,5–16+ months). 1 pt received allogenic bone marrow transplantation in CR. During this first part of the trial 10 deaths were recorded with a 12 months estimated survival of 52% (95%CI: 26–77): 2 deaths were due to disease progression; 3 occurred early in the course of the disease ( 2 CNS haemorrhage and 1 after splenectomy ); 3 after achieving initial hematologic response ( 1 relapse, 1 septic shock, 1 hepatitis) 2 because of refractory relapse after achieving initial CCR. Imatinib combined with the classical 3 + 7 induction protocol produce a high rate of haematological remissions in myeloid BC pts. Daunorubicin dosage should be tapered to 30 mg/m² per day to avoid excessive toxicity. Additional pts are currently under treatment with this dosage in order to confirm this recommendation. An update of this trial will be presented.

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 ofETV6-NTRK3 fusion gene in secretory breast carcinoma

2004 ◽  
Vol 40 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Nikita Makretsov ◽  
May He ◽  
Malcolm Hayes ◽  
Stephen Chia ◽  
Doug E. Horsman ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Breast Carcinoma ◽  
Fluorescence In Situ Hybridization ◽  
Fusion Gene ◽  
Hybridization Study ◽  
Secretory Breast Carcinoma
Sign in / Sign up

Export Citation Format

Share Document