Acute myeloid leukemia carrying ETV6 mutations: biologic and clinical features

Zhou, Fang; Chen, Baoan

doi:10.1080/10245332.2018.1482051

Cited by 13 publications

(10 citation statements)

References 31 publications

(40 reference statements)

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“…Although other, non-NTRK ETV6-based fusions have been long reported to play a role in leukemogenesis [ 42 , 48 – 51 ], an EN fusion was first reported in 1999 by Eguchi et al [ 52 , 53 ] in a 59-year-old female with AML-M2 using fluorescence in situ hybridization (FISH). They identified two variants of the fusion with FISH ( Fig.…”

Section: Ntrk Receptor Alterations and Their Role In Cancer Developmementioning

confidence: 99%

Revisiting NTRKs as an emerging oncogene in hematological malignancies

et al. 2019

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NTRK fusions are dominant oncogenic drivers found in rare solid tumors. These fusions have also been identified in more common cancers, such as lung and colorectal carcinomas, albeit at low frequencies. Patients harboring these fusions demonstrate significant clinical response to inhibitors such as entrectinib and larotrectinib. Although current trials have focused entirely on solid tumors, there is evidence supporting the use of these drugs for patients with leukemia. To assess the broader applicability for Trk inhibitors in hematological malignancies, this review describes the current state of knowledge about alterations in the NTRK family in these disorders. We present these findings in relation to the discovery and therapeutic targeting of BCR-ABL1 in chronic myeloid leukemia. The advent of deep sequencing technologies has shown that NTRK fusions and somatic mutations are present in a variety of hematologic malignancies. Efficacy of Trk inhibitors has been demonstrated in NTRK-fusion positive human leukemia cell lines and patient-derived xenograft studies, highlighting the potential clinical utility of these inhibitors for a subset of leukemia patients.

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Section: Ntrk Receptor Alterations and Their Role In Cancer Developmementioning

confidence: 99%

Revisiting NTRKs as an emerging oncogene in hematological malignancies

et al. 2019

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“…ETV is a critical transcriptional regulator involved in hematopoiesis, vascular development, and chromosomal translocations linked with hematological malignancies ( 58 ). Meanwhile, it has been reported that the ETV6 mutations collaborate with other mutations to build their own network structure, which would stimulate the self-renewal of leukemia stem cells ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

Mariam

Norhidayah²,

Zulaikha³

et al. 2022

Front. Oncol.

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The emergence of additional chromosome abnormalities (ACAs) in chronic myeloid leukemia (CML) patients during treatment with a tyrosine kinase inhibitor (TKI) regime is generally associated with resistance to treatment and a sign of disease progression to accelerated phase or blast phase. We report the type, frequency, and differential prognostic impact of stratified ACAs with treatment response in 251 Malaysian CML patients undergoing TKI therapy. ACAs were observed in 40 patients (15.9%) of which 7 patients (17.5%) showed ACAs at time of initial diagnosis whereas 33 patients (82.5%) showed ACAs during the course of IM treatment. In order to assess the prognostic significance, we stratified the CML patients with ACAs into four groups, group 1 (+8/+Ph), group 2 (hypodiploidy), group 3 (structural/complex abnormalities); group 4 (high-risk complex abnormalities), and followed up the disease outcome of patients. Group 1 and group 2 relatively showed good prognosis while patients in group 3 and group 4 had progressed or transformed to AP or blast phase with a median survival rate of 12 months after progression. Novel ACAs consisting of rearrangements involving chromosome 11 and chromosome 12 were found to lead to myeloid BP while ACAs involving the deletion of 7q or monosomy 7 led toward a lymphoid blast phase. There was no evidence of group 2 abnormalities (hypodiploidy) contributing to disease progression. Compared to group 1 abnormalities, CML patients with group 3 and group 4 abnormalities showed a higher risk for disease progression. We conclude that the stratification based on individual ACAs has a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guide the treatment of CML patients at diagnosis and during treatment.

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“…Marrow eosinophilia has also been described in rare forms of myelomonocytic leukemia. ETV6 fusions with different tyrosine kinase proteins including ABL 1, FLT 3, JAK 2, and FGFR 3 are associated with leukemogenesis and hypereosinophilia [ 6 ]. In these cases, prognosis has largely been determined by the fusion partner and responsiveness to different targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

A Case of Acute Eosinophilic Leukemia with a Novel PHF6 Mutation

Lipof

Huselton

Zent

et al. 2021

Case Reports in Hematology

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Acute eosinophilic leukemia (AEL) is a rare form of acute myeloid leukemia (AML) that requires prompt exclusion of reactive etiologies of eosinophilia and identification of an underlying acute myeloid neoplasm. Myeloid neoplasms with prominent eosinophilia often have rearrangements in the platelet-derived growth factor receptor α (PDGFRA) or β (PDGFRB) or are associated with core-binding factor AML. In this report, we describe a 35-year-old male presenting with chest discomfort and altered mental status, found to have marked leukocytosis with eosinophilic predominance and an elevated blast count. Bone marrow aspirate and biopsy findings were morphologically consistent with AEL. Fluorescence in situ hybridization (FISH) and standard karyotype analysis did not reveal any abnormalities, and mutation analysis using next generation sequencing (NGS) revealed a pathogenic mutation in PHF6. Cardiac work-up revealed findings suggestive of eosinophilic myocarditis. High-dose glucocorticoid therapy was initiated followed by standard intensive induction chemotherapy with cytarabine and idarubicin. He experienced a rapid reduction in peripheral blood eosinophil and blast count and was found to be in a complete remission at the time of his postinduction bone marrow examination. He underwent allogeneic stem cell transplantation with a matched sibling donor after consolidative high-dose cytarabine and remains in remission at the time of this report, 6 months following his initial diagnosis. The rarity of this condition has resulted in a paucity of data to guide management. Additional studies are needed to better characterize this entity and inform optimal management strategies to attain a long-term sustained remission in these patients.

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Acute myeloid leukemia carrying ETV6 mutations: biologic and clinical features

Abstract: Future researches are needed to explain how ETV6 mutations act within the microenvironment of leukemic cells and how it affects the progression of leukaemia.

Cited by 13 publications

References 31 publications

Revisiting NTRKs as an emerging oncogene in hematological malignancies

Revisiting NTRKs as an emerging oncogene in hematological malignancies

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

A Case of Acute Eosinophilic Leukemia with a Novel PHF6 Mutation

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