Chronic phase of <i>ETV6‐ABL1</i> positive CML responds to imatinib

Kawamata, Norihiko; Dashti, Azadeh; Lu, Daning; Miller, Becky; Koeffler, H. Phillip; Schreck, Rhona; Moore, Stephen; Ogawa, Seishi

doi:10.1002/gcc.20593

Cited by 22 publications

(29 citation statements)

References 7 publications

(3 reference statements)

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“…1,18,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Standard diagnostics, including molecular genetics, karyotyping and fluorescence in-situ hybridization (FISH) were performed according to the standard practice of the local diagnostic laboratories. Basic clinical/outcome data were collected from treating centers.…”

Section: Patientsmentioning

confidence: 99%

Characterization of leukemias with ETV6-ABL1 fusion

et al. 2016

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T o characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with tyrosine kinase inhibitors should be considered for patients with this fusion.

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Section: Patientsmentioning

confidence: 99%

Characterization of leukemias with ETV6-ABL1 fusion

et al. 2016

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“…[1][2][3][4][5][6][7][8][9] The ETV6-ABL1 fusion gene has also been identified in 3 patients with chronic myeloproliferative neoplasms other than "chronic myeloid leukemia" (cMPN) as well as 7 patients with BCR-ABL1 negative acute lymphoblastic leukemia and 4 patients with acute myeloid leukemia. 10,11 Of the 9 cases of ETV6-ABL1 + chronic myeloid leukemia, only 2 were treated with a TKI in chronic phase 4,5 and only one of these reached a complete remission with a modest follow up of seven months (no molecular monitoring was performed). 4 Among the other published ETV6-ABL1 + reports, one patient was treated with a second generation TKI for a relapsed cMPN.…”

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confidence: 99%

“…10,11 Of the 9 cases of ETV6-ABL1 + chronic myeloid leukemia, only 2 were treated with a TKI in chronic phase 4,5 and only one of these reached a complete remission with a modest follow up of seven months (no molecular monitoring was performed). 4 Among the other published ETV6-ABL1 + reports, one patient was treated with a second generation TKI for a relapsed cMPN. 12 We provide the first molecular documentation of sustained remission of ETV6-ABL1 + chronic phase "chronic myeloid leukemia" (CML requires a BCR-ABL1 fusion according to the most recent 2008 WHO classification) to TKI.…”

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confidence: 99%

ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibition

et al. 2010

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“…ETV6 is the only non-BCR fusion partner for ABL reported to date, and it is thought to have TK activity similar to BCR/ABL. In the last years, few case reports focused on the efficacy of imatinib in chronic-phase MPNs and ETV6-ABL rearrangement, with cytogenetic and molecular remissions but short follow-up [5,7]. Our patient had an excellent response to imatinib though complicated by an unusual olfactory toxicity (dysosmia) that, to the best of our knowledge, has never been reported with imatinib.…”

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confidence: 66%

Long-term efficacy and safety of nilotinib therapy after imatinib failure in eosinophilic myeloproliferative neoplasm and ETV6-ABL rearrangement

et al. 2015

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Dear Editor, The ETV6 gene, previously known as TEL, is a member of the ETS family of transcription factors located at 12p13. Its role in leukemogenesis was initially estabilished as a fusion partner to the PDGFR-beta gene in a case of chronic myelomonocytic leukemia with t (5;12)(q33;p13) [1]. The ETV6-ABL gene product has been demonstrated to have tyrosine kinase activity remarkably similar to that of BCR-ABL, despite the fusion partners for ABL being completely different [2]. Several studies proved the efficacy of imatinib for patients with hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL), especially in those who express the FIP1L1-PDGFRα fusion gene [3][4][5]. As development of resistance or intollerance to Imatinib in these patients may parallel that seen in chronic myeloid leukemia (CML), the evaluation of second-generation tyrosine kinase inhibitors (TKIs), such as nilotinib, has been reported [6]. However, to date, little is known on long-term efficacy and safety of secondgeneration TKIs after imatinib failure in patients with eosinophilic neoplasms.A 65-year-old male was found to have hemoglobin 13.0 g/dL, platelets 302×10 3 /μL, leukocytes 16.7×10 3 /μL, with 65 % neutrophilis, 3 % metamyelocytes, 3 % myelocytes, 10 % eosinophils, 8 % basophils, 8 % lymphocytes, and 3 % monocytes. The physical exam was negative. Bone marrow biopsy and aspirate were consistent with a chronic phase myeloproliferative neoplasm (MPN). Karyotype was 46,XY,t(9;12)(q34;p12); molecular analysis was negative for BCR/ABL and for rearrangements involving PDGFRα and β and FIP1L1 gene, while showing a fusion between ETV6 and ABL genes.

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Chronic phase of ETV6‐ABL1 positive CML responds to imatinib

Cited by 22 publications

References 7 publications

Characterization of leukemias with ETV6-ABL1 fusion

Characterization of leukemias with ETV6-ABL1 fusion

ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibition

Long-term efficacy and safety of nilotinib therapy after imatinib failure in eosinophilic myeloproliferative neoplasm and ETV6-ABL rearrangement

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