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

Abstract

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.

Acute myeloid leukemia with a novel AKAP9::PDGFRA fusion transformed from essential thrombocythemia: A case report and mini review

“…The FIP1L1::PDGFRA fusion has been proposed as a surrogate marker for the diagnosis of chronic eosinophilic leukemia, hypereosinophilic syndrome, and systemic mastocytosis, making the tyrosine kinase inhibitor imatinib a treatment alternative [ 38 , 39 ]. FIP1L1::PDGFRA fusion is also associated with eosinophilia-associated AML patients [ [13] , [14] , [15] ]. Shah et al reported a patient in whom FIP1L1::PDGFRA was discovered during evolution from chronic myelomonocytic leukemia to AML that was resistant to conventional therapy; however, imatinib treatment resulted in a durable complete remission [ 40 ].…”

“…Shah et al reported a patient in whom FIP1L1::PDGFRA was discovered during evolution from chronic myelomonocytic leukemia to AML that was resistant to conventional therapy; however, imatinib treatment resulted in a durable complete remission [ 40 ]. In another unusual case, an AML patient in relapse was found to have both DEK::NUP214 and FIP1L1::PDGFRA fusions without marked eosinophilia in the PB or BM [ 15 ]. At no time during her disease course did the patient reported here have eosinophilia.…”

“…The WHO now designates groups of AML patients based on defining genetic abnormalities that include the following fusions such as RUNX1::RUNX1T1, CBFB::MYH11, PML::RARA , among others [ 6 ]. Multiple other recurrent fusion genes that have also been identified in AML patients, many of which have been associated with prognosis and response to therapy [ 3 , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] ]. Here, we present a case with a long history of essential thrombocythemia (ET) with a CALR mutation, which transformed to AML characterized by a novel AKAP9::PDGFRA fusion gene.…”

Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia

“…Gene rearrangements of PDGFRA and PDGFRB have been reported in AMLs. 44,45 Further molecular aberrations or crosstalk between PDGFR and FLT3 might be involved in DNA methylation changes.…”