Complete and long‐lasting cytologic and molecular remission of <i><scp>FIP</scp>1L1‐<scp>PDGFRA</scp>‐</i>positive acute eosinophil myeloid leukaemia, treated with low‐dose imatinib monotherapy

Barraco, Daniela; Carobolante, Francesca; Candoni, Anna; Simeone, Ester; Piccaluga, Pierpaolo; Tabanelli, Valentina; Fanin, Renato

doi:10.1111/ejh.12272

Cited by 11 publications

(8 citation statements)

References 12 publications

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“…POU2F1 , a novel partner gene, is a transcription factor, and the resulting fusion gene will have an intact PDGFRA kinase domain, potentially causing a differently regulated kinase activity with sensitivity to TKIs. The patients with PDGFRA gene fusion were reported to show good response to TKIs, proving additional clinical significance of the testing.…”

Section: Discussionmentioning

confidence: 95%

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Kim

Lee

et al. 2020

Hematological Oncology

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Identification of gene fusion is an essential part in the management of patients with acute leukemia, not only for diagnosis but also in predicting the treatment outcome and selecting appropriate treatment. Adopting next-generation sequencing (NGS) technology for identification of gene fusion in patients with acute leukemia can be a good alternative to conventional tests. In the present study, the NGS RNA fusion gene panel test was applied to diagnostic samples of patients with acute leukemia to identify fusion genes more efficiently. Among 134 patients with acute leukemia, 53 gene fusions were detected in 52 patients. In addition to the recurrent gene fusions specified in the WHO diagnostic criteria, 11 rare or novel gene fusions were identified. Of those, two were gene fusions associated with Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), two were novel gene fusions, three were gene fusions with novel partner genes, and six were rare gene fusions from previous reports. We confirmed the clinical utility of the NGS test in identifying clinically significant gene fusions such as gene fusions involving KMT2A that has a large number of partners. Notably, Ph-like ALL-associated gene fusions could be easily identified despite the wide variety of genes involved. The results from the present study may contribute toward a better understanding of the genomic landscape of acute leukemia as well as patient management. K E Y W O R D Sacute leukemia, next-generation sequencing, RNA gene fusion detection

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Section: Discussionmentioning

confidence: 95%

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Kim

Lee

et al. 2020

Hematological Oncology

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“…Numerous studies have revealed that imatinib administration achieves complete hematological remission in patients diagnosed with AML, myeloid sarcoma, and B and T cell leukemia/lymphoma associated with FIP1L1-PDGFRA arrangement (2,3,14). FIP1L1-PDGFRA fusion results in constitutive activation of tyrosine kinase enzymes by disrupting the autoinhibitory juxtamembrane domain of PDGFRA (8).…”

Section: Discussionmentioning

confidence: 99%

“…In 2016, the World Health Organization defined myeloid and lymphoid neoplasms with eosinophilia and abnormalities of platelet-derived growth factor receptor α (PDGFRA), platelet-derived growth factor receptor β (PDGFRB), fibroblast growth factor receptor 1 or pericentriolar material 1-janus kinase 2 (1,2). Although fusion genes are most frequently detected in patients with chronic clonal eosinophilic neoplasms, they are occasionally detected in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (3).…”

Section: Introductionmentioning

confidence: 99%

Imatinib therapy in acute myeloid leukemia with DEK‑NUP214 and FIP1L1‑PDGFRA rearrangement: A case report

Yang

Lin

et al. 2020

Oncol Lett

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The fusion product of FIP1-like-1 (FIP1L1) and platelet-derived growth factor receptor α (PDGFRA) gene rearrangement is a tyrosine kinase oncoprotein sensitive to imatinib. This gene rearrangement characterizes a novel clinico-biological class of myeloid and lymphoid neoplasms with eosinophilia and PDGFRA abnormalities. The DEK proto-oncogene (DEK) and nucleoporin 214 (NUP214) rearrangement is rare in patients with acute myeloid leukemia (AML); therefore, the coexistence of DEK-NUP214 and FIP1L1-PDGFRA rearrangements in patients with AML is extremely rare. The present study presents a rare relapse case of a patient with AML with DEK-NUP214 and FIP1L1-PDGFRA rearrangements, without marked eosinophilia in the peripheral blood or bone marrow. Low-dose imatinib monotherapy without intensive chemotherapy was used to achieve complete hematological remission.

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“…Other rare cytogenetic abnormalities involving PDGFRα reported in hematolymphoid neoplasms include t(4;22)(q12;q11), ins(9;4)(q33;q12q25), t(2;4) (p24;q12) and t(4;12)(q12;p13) [27][28][29][30]. These patients respond well to treatment with imatinib [8,31,32] development of clonal eosinophilia during the course of leukemia and response to treatment with imatinib. Zota et al, [33] reported a case of CMML in which a clone with FIP1L1/PDGFRα fusion transiently developed with concurrent PB and BM eosinophilia and regressed with imatinib treatment, whereas the initial CMML clone persisted and led to fatality.…”

Section: Discussionmentioning

confidence: 99%

A unique rearrangement of PDGFRα and ETV6 in a patient with acute myeloid leukemia with myelodysplasia-related changes progressed from chronic myelomonocytic leukemia

Koduru¹,

Guruju²,

Patel³

et al. 2016

Hematol Leuk

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Platelet derived growth factor receptor alpha (PDGFRα) undergoes different types of rearrangements creating fusion genes in myeloid neoplasms. Cryptic deletion at 4q12 creating FIP1L1/PDGFRα fusion is the most frequent and is associated with hypereosinophilia. The other infrequent but recurrent abnormality involving PDGFRα seen in myeloid neoplasms is a t(4;12)(q12;p13), which creates a fusion gene with ETV6 and activates ETV6 via the tyrosine kinase domain of the PDGFRα. We characterized a new t(4;12;6) translocation which developed during transformation to acute myeloid leukemia (AML) in a patient with chronic myelomonocytic leukemia (CMML). Standard G-band karyotype analysis and fluorescence in-situ hybridization study (FISH) analysis with a tricolor 4q12 probe and ETV6 was performed on the bone marrow (BM) involved by AML. The karyotype showed a t(4;12;6)( q12;p13;p21.3). FISH showed fusion between PDGFRα and ETV6. Patient did not respond to treatment with imatinib or to standard induction chemotherapy for AML, and expired 11 months from diagnosis. This is the first report of a variant t(4;12;6) and ETV6/PDGFRα fusion that developed during transition from CMML to AML and did not respond to imatinib.

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Complete and long‐lasting cytologic and molecular remission of FIP1L1‐PDGFRA‐positive acute eosinophil myeloid leukaemia, treated with low‐dose imatinib monotherapy

Cited by 11 publications

References 12 publications

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Imatinib therapy in acute myeloid leukemia with DEK‑NUP214 and FIP1L1‑PDGFRA rearrangement: A case report

A unique rearrangement of PDGFRα and ETV6 in a patient with acute myeloid leukemia with myelodysplasia-related changes progressed from chronic myelomonocytic leukemia

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