Chronic Myelogenous Leukemia with the e6a2 &lt;i&gt;BCR-ABL&lt;/i&gt; and Lacking Imatinib Response: Presentation of Two Cases

Vefring, Hege K.; Gruber, Franz; Wee, Line; Hovland, Randi; Hjorth‐Hansen, Henrik; Dahl, Tobias Gedde; Meyer, Peter

doi:10.1159/000230037

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Data reported so far indicate that the course of disease associated with e6a2a is particularly aggressive both in chronic and acute leukemias. In fact, within CML cases harboring this transcript, 6/17 developed an accelerated or blastic phase [6, 14, 17–20]. Furthermore, there was a prevalence of males on female (ratio 14:3) and the median age at diagnosis was 48 years old (range 18–76 years).…”

Section: Discussionmentioning

confidence: 99%

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

et al. 2019

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BackgroundPhiladelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis.Case presentationA 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2′-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection.ConclusionThe atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.

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Section: Discussionmentioning

confidence: 99%

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

et al. 2019

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“…This transcript type has also been reported in t(9;22)-positive acute myeloid leukemia (AML) and transformed chronic myelomonocytic leukemia [ 7 – 9 ]. Although responses to imatinib have been reported [ 10 , 11 ], several cases of ABL1 kinase domain mutation-associated imatinib resistant, e6a2 BCR-ABL1 CML have been documented [ 12 , 13 ] with limited information on the efficacy of front line second-generation TKIs in this genotype. As e6a2 BCR-ABL1 CML is associated with aggressive disease, allogeneic stem cell transplantation (ASCT) remains the only curative option and in such circumstances conventional AML therapy has been combined with a second-generation TKI as a bridge to ASCT [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

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

Crampe

Haslam

Groarke

et al. 2017

Case Reports in Hematology

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A minority of chronic myeloid leukemia patients (CML) express a variety of atypical BCR-ABL1 fusion variants and, of these, the e6a2 BCR-ABL1 fusion 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 e6a2 BCR-ABL1 genotype. Moreover, molecular monitoring is only sporadically performed in CML patients with atypical BCR-ABL1 fusion 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 single ASXL1 mutation cooperating with an e6a2 BCR-ABL1 fusion 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 e6a2 BCR-ABL1 transcripts. This case emphasizes the requirement for molecular monitoring in CML patients with atypical BCR-ABL1 fusion transcripts and emphasizes that comprehensive sequencing has the potential to identify targets for novel therapies in CML patients with advanced disease.

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“… 7 Schnittger [1] 48/M CML-CP e6a2 Imatinib, HU, dasatinib Imatinib: disease progression with clonal evolution and resistence mutations Death from blast crisis 10 mo. Dasatinib: Initial hematologic and cytogenetic remission followed by blast crisis and new resistance mutation 8 Vefring [7] 42/M CML-AP e6a2 Imatinib, ASCT, dasatinib Imatinib: persistent disease Developed myeloid sarcoma (CML-BP) after ASCT 45 mo. Dasatinib: effective on subsequent myeloid sarcoma Death from hematemesis 9 Vefring [7] 48/M CML-CP e6a2 Imatinib, CDA, αIFN, ASCT Disease progression Hematologic remission after ASCT Alive at 62 mo.…”

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confidence: 99%

“… Dasatinib: Initial hematologic and cytogenetic remission followed by blast crisis and new resistance mutation 8 Vefring [7] 42/M CML-AP e6a2 Imatinib, ASCT, dasatinib Imatinib: persistent disease Developed myeloid sarcoma (CML-BP) after ASCT 45 mo. Dasatinib: effective on subsequent myeloid sarcoma Death from hematemesis 9 Vefring [7] 48/M CML-CP e6a2 Imatinib, CDA, αIFN, ASCT Disease progression Hematologic remission after ASCT Alive at 62 mo. 10 Langabeer [8] 36/M CML-CP e6a2, e1a2 Imatinib, nilotinib, ASCT Imatinib: progression to AP with clonal evolution Complete molecular remission Alive at 28 mo.…”

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A case of acute myeloid leukemia with e6a2 BCR-ABL fusion transcript acquired after progressing from chronic myelomonocytic leukemia

Yao

Douer

Wang

et al. 2017

Leukemia Research Reports

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Philadelphia (Ph) chromosome is a cytogenetic hallmark of chronic myeloid leukemia (CML). Most patients with CML harbor either the e13a2 or e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. We report a patient with chronic myelomonocytic leukemia (CMML), initially Ph chromosome negative at presentation, with rapid disease progression to acute myeloid leukemia (AML) and appearance of Ph chromosome and BCR-ABL e6a2, a very uncommon fusion transcript. The AML was refractory to treatment with subsequent emergence and dominance of a Ph negative leukemic clone. The patient expired shortly after disease progression.

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Chronic Myelogenous Leukemia with the e6a2 <i>BCR-ABL</i> and Lacking Imatinib Response: Presentation of Two Cases

Cited by 11 publications

References 33 publications

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

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

A case of acute myeloid leukemia with e6a2 BCR-ABL fusion transcript acquired after progressing from chronic myelomonocytic leukemia

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