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

Abstract

Myeloproliferative neoplasms associated with FIP1L1-PDGFR rearrangements represent a rare subset of myeloid and lymphoid malignancies, characterised by the presence of eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 genes. The fusion product of such genes is a tyrosine kinase oncoprotein sensitive to imatinib, which to date results to be the standard of care for FIP1L1-PDGFRA-positive chronic myeloproliferative disorders with eosinophilia. However, the coexistence of FIP1L1-PDGFRA rearrangement associated with acute myeloid leukaemia is extremely rare. Here, we report a rare case of FIP1L1-PDGFRA-positive acute myeloid leukaemia, with marked peripheral blood and bone marrow eosinophilia, treated with low dose of imatinib monotherapy, achieving a rapid and long-lasting complete cytologic and molecular remission, without need for intensive chemotherapy.

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

“…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.…”

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

“…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).…”

“…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).…”

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

“…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.…”