scholarly journals Chronic Myeloid Leukemia with an e6a2BCR-ABL1Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Mireille Crampe ◽  
Karl Haslam ◽  
Emma Groarke ◽  
Eileen Kelleher ◽  
Derville O’Shea ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Blast Crisis ◽  
Fusion Transcript ◽  
Molecular Monitoring ◽  
Disease Response ◽  
Fusion Transcripts ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

A minority of chronic myeloid leukemia patients (CML) express a variety of atypicalBCR-ABL1fusion variants and, of these, the e6a2BCR-ABL1fusion is generally associated with an aggressive disease course. Progression of CML to blast crisis is associated with acquisition of additional somatic mutations yet these events have not been elucidated in patients with the e6a2BCR-ABL1genotype. Moreover, molecular monitoring is only sporadically performed in CML patients with atypicalBCR-ABL1fusion transcripts due to lack of consensus approaches or standardization. A case of CML is described in which comprehensive molecular analysis, including targeted next-generation sequencing, revealed a singleASXL1mutation cooperating with an e6a2BCR-ABL1fusion transcript at blast crisis. A quantitative molecular monitoring approach was devised and adopted that reflected the disease response from initial treatment through allogeneic stem cell transplantation which resulted in undetectable e6a2BCR-ABL1transcripts. This case emphasizes the requirement for molecular monitoring in CML patients with atypicalBCR-ABL1fusion transcripts and emphasizes that comprehensive sequencing has the potential to identify targets for novel therapies in CML patients with advanced disease.

scholarly journals The Role of Monitoring the Bcr-Abl Transcript Levels in the Management of Patients with Chronic Myeloid Leukemia

2013 ◽  
Vol 59 (2) ◽  
pp. 71-74
Author(s):  
Aliz-Beáta Tunyogi ◽  
I Benedek ◽  
Judit Beáta Köpeczi ◽  
Erzsébet Benedek ◽  
Enikő Kakucs ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Chronic Gvhd ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Molecular Monitoring ◽  
Hematopoietic Stem ◽  
Transcript Levels

Abstract Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder; the molecular hallmark of the disease is the BCR-ABL gene rearrangement, which usually occurs as the result of a reciprocal translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors (TKI) were the first drugs that targeted the constitutively active BCR-ABL kinase and it have become the standard frontline therapy for CML. Monitoring the treatment of CML patients with detection of bcr-abl transcript levels with real time qualitative polymerase chain reaction (RQ-PCR) is essential in evaluating the therapeutic response. Material and method: At the Clinical Hematology and BMT Unit Tîrgu Mureș, between 2008-2011, we performed the molecular monitoring of bcr-abl transcript levels with RQ-PCR in 16 patients diagnosed with CML. Results: We have 11 patients on imatinib treatment who achieved major molecular response. One patient lost the complete molecular response after 5 years of treatment. Two patients in blast crisis underwent allogeneic hematopoietic stem cell transplantation from identical sibling donors. The first patient is in complete molecular remission after 4 years of the transplant with mild chronic GVHD. The other patient had an early relapse with treatment refractory disease and died from evolution of the disease. Three patients with advanced phases of the disease present increasing transcript levels. We performed the dose escalation, and for two of them the switch to the second generation of TKI. Conclusions: Regular molecular monitoring of individual patients with CML is clearly desirable. It allows for a reassessment of the therapeutic strategy in cases of rising levels of BCR-ABL as an early indication of loss of response.

scholarly journals IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis

Leukemia ◽  
2010 ◽  
Vol 25 (1) ◽  
pp. 178-181 ◽  
Author(s):  
S Soverini ◽  
J Score ◽  
I Iacobucci ◽  
A Poerio ◽  
A Lonetti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Blast Crisis

scholarly journals Mutational Phasing: Clinical Relevance in Tyrosine Kinase Domain Mutations Using Next Generation Sequencing in Chronic Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4269-4269
Author(s):  
Seema S. Bhatwadekar ◽  
Parth Shah
Keyword(s):  
Next Generation Sequencing ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Mutation Analysis ◽  
Clinical Relevance ◽  
Myeloid Leukemia ◽  
Sanger Sequencing ◽  
Blast Crisis ◽  
Kinase Domain ◽  
Generation Sequencing

Abstract Background: Tyrosine kinase mutation analysis in BCR/ABL1 gene is important for management of patients with chronic myeloid leukemia. Sanger Sequencing has been the mainstay for testing with Next Generation Sequencing (NGS) now becoming the primary technology. In this study we show a comparison between NGS versus Sanger Seqencing based ABL kinase domain mutation analysis with a likely trend of clinical relevance based on a compound versus polyclonal state of mutational distribution which may also need to be considered for patient management and therapy. Methodology: A total of 213 Imatinib-resistant patients with CML for BCR-ABL1 mutation analysis were processed on both technologies.Initial blood counts were assessed and RNA was extractedfollowed by cDNA conversion. NGS libraries were prepared with 400bp multiplexed amplicons to allow optimal phasing. Results: 179 samples were negative by both technologies. A total of only 20 samples were positive and concordant by both technologies(58.2%). Mutations in 14 other samples however were only detected in NGS(41.17%). In these 14 samples (41.17%), NGS was able to detect 23 mutations with mutation frequencies of 3-28%, which were missed by Sanger. Conclusions: Moreover 11/34 patients had 2 or >2 mutations. An inhouse script delineated mutations as compound or polyclonal from NGS data. 2/11 cases demonstrated compound mutations (Mutations in the same clone) while 7/11 cases were polyclonal per NGS. Sanger sequencing cannot differentiate between polyclonal and compound mutations. 2/11 cases appeared to have polyclonal and compound mutations. 4/11 patients presented in a blast crisis or accelerated phase CML. Interestingly, most of these patients hadat leasttwo mutations and were polyclonal(3/4). Significantly previously archived samples patients with polyclonal mutations showed polyclonality at extremely low frequency percentages in initial samples. None of the single mutation patients had presented in a blast crisis or an accelerated phase. Disclosures No relevant conflicts of interest to declare.

Somatic mutations ofPHF6in patients with chronic myeloid leukemia in blast crisis

2012 ◽  
Vol 54 (3) ◽  
pp. 671-672 ◽  
Author(s):  
Xianmin Li ◽  
Hong Yao ◽  
Zixing Chen ◽  
Qinrong Wang ◽  
Yun Zhao ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Blast Crisis

scholarly journals PML-RARA Fusion Transcripts Detectable 8 Months prior to Promyelocytic Blast Crisis in Chronic Myeloid Leukemia

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Stephanie Wolanin ◽  
Robert K. McCall ◽  
Mark J. Pettenati ◽  
Michael W. Beaty ◽  
Giovanni Insuasti-Beltran ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Age At Onset ◽  
Chronic Phase ◽  
Leukemic Cells ◽  
Time Interval ◽  
Male Predominance ◽  
Fusion Transcripts ◽  
Clonal Progression

Promyelocytic blast crisis arising from chronic myeloid leukemia (CML) is rare. We present a 40-year-old male who developed promyelocytic blast crisis 17 months after CML diagnosis, confirmed by the presence of the t(15;17) and t(9;22) translocations in the leukemic cells. Preserved nucleic acids from routine BCR-ABL1 testing provided a unique opportunity to evaluate clonal progression over time. Retrospective analysis demonstrated PML-RARA fusion transcripts were first detectable 8 months prior to blast crisis presentation. A review of 21 cases of promyelocytic blasts crisis published in the literature reveals a male predominance with earlier age at onset as compared to females. Interestingly, TKI therapy during chronic phase did not impact the time interval between diagnosis and promyelocytic blast crisis. Treatment with standard acute promyelocytic leukemia regimens provides more favorable outcomes with complete molecular remission. Although rare, it is important to consider a promyelocytic blast crisis when evaluating for transformation of CML due to its effective treatment with specific therapies.

Blast crisis of chronic myeloid leukemia with plasmacytoid dendritic cell phenotype associated with a rare fusion transcript, e13a3 BCR–ABL1

2019 ◽  
Vol 60 (12) ◽  
pp. 3090-3091
Author(s):  
Danmei Xu ◽  
Simone Claudiani ◽  
Kikkeri Naresh ◽  
Stuart Mucklow ◽  
Pratap Neelakantan ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Plasmacytoid Dendritic Cell ◽  
Fusion Transcript ◽  
Cell Phenotype

Meningeal Leukemia following Lymphoid Blast Crisis in Chronic Myeloid Leukemia: Therapeutic Implications

1982 ◽  
Vol 68 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Mario Cazzola ◽  
Giulio Nalli ◽  
Ercole Brusamolino ◽  
Maurizio Daccò ◽  
Angela Ghizzi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Early Prevention ◽  
Therapeutic Implications ◽  
Therapeutic Protocol ◽  
Meningeal Leukemia

Five of 40 patients with chronic myeloid leukemia (CML) had lymphoid blast crisis and 4 of them achieved complete remission of metamorphosis with vincristine and prednisone. While in hematologic remission, two of these subjects developed meningeal leukemia. Clinical and biologic data indicated that the course of the disease after lymphoid blast crisis was very similar to that of acute lymphoblastic leukemia (ALL). It is suggested that patients with CML who develop lymphoid blast crisis should be treated with an intensive therapeutic protocol including early prevention of meningeal leukemia.

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