Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report
Myeloproliferative neoplasm (MPN) with eosinophilia associated with <i>FIP1L1-PDGFRA</i> is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurr...
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MDPI AG
2025-03-01
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| author | Sıdıka Gülkan Özkan Ali Kimiaei Seyedehtina Safaei Mutlu Karkucak Mustafa Nuri Yenerel Aslı Yüksel Öztürkmen Burak Alp Hasan Atilla Özkan |
| author_facet | Sıdıka Gülkan Özkan Ali Kimiaei Seyedehtina Safaei Mutlu Karkucak Mustafa Nuri Yenerel Aslı Yüksel Öztürkmen Burak Alp Hasan Atilla Özkan |
| author_sort | Sıdıka Gülkan Özkan |
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| description | Myeloproliferative neoplasm (MPN) with eosinophilia associated with <i>FIP1L1-PDGFRA</i> is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent <i>FIP1L1-PDGFRA T674I</i> and <i>PTPN11</i> (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with <i>FIP1L1-PDGFRA T674I</i>-positive eosinophilic disorder, especially when compounded by the <i>PTPN11</i> mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease. |
| format | Article |
| id | doaj-art-ea0d39e1ee0a49c188c6d09e0575e7b3 |
| institution | DOAJ |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj-art-ea0d39e1ee0a49c188c6d09e0575e7b32025-08-20T02:42:25ZengMDPI AGLife2075-17292025-03-0115350510.3390/life15030505Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case ReportSıdıka Gülkan Özkan0Ali Kimiaei1Seyedehtina Safaei2Mutlu Karkucak3Mustafa Nuri Yenerel4Aslı Yüksel Öztürkmen5Burak Alp6Hasan Atilla Özkan7Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Bahçeşehir University, 34734 Istanbul, TurkeyDepartment of Internal Medicine, Division of Hematology, Faculty of Medicine, Bahçeşehir University, 34734 Istanbul, TurkeyDepartment of Internal Medicine, Division of Hematology, Faculty of Medicine, Bahçeşehir University, 34734 Istanbul, TurkeyGenetic Diseases Assessment Center, İstinye University, 34010 Istanbul, TurkeyDepartment of Internal Medicine, Division of Hematology, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, TurkeyDepartment of Internal Medicine, Division of Hematology, Sivas Numune Hospital, 58060 Sivas, TurkeyAdult Hematology and Bone Marrow Transplantation Unit, Medical Park Göztepe Hospital, 34732 Istanbul, TurkeyDepartment of Internal Medicine, Division of Hematology, Faculty of Medicine, Bahçeşehir University, 34734 Istanbul, TurkeyMyeloproliferative neoplasm (MPN) with eosinophilia associated with <i>FIP1L1-PDGFRA</i> is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent <i>FIP1L1-PDGFRA T674I</i> and <i>PTPN11</i> (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with <i>FIP1L1-PDGFRA T674I</i>-positive eosinophilic disorder, especially when compounded by the <i>PTPN11</i> mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease.https://www.mdpi.com/2075-1729/15/3/505eosinophilic disorder<i>FIP1L1-PDGFRA T674I</i> mutationimatinib resistance<i>PTPN11</i> mutationmyeloproliferative neoplasm |
| spellingShingle | Sıdıka Gülkan Özkan Ali Kimiaei Seyedehtina Safaei Mutlu Karkucak Mustafa Nuri Yenerel Aslı Yüksel Öztürkmen Burak Alp Hasan Atilla Özkan Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report Life eosinophilic disorder <i>FIP1L1-PDGFRA T674I</i> mutation imatinib resistance <i>PTPN11</i> mutation myeloproliferative neoplasm |
| title | Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report |
| title_full | Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report |
| title_fullStr | Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report |
| title_full_unstemmed | Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report |
| title_short | Therapeutic Challenges and Emerging Strategies for <i>T674I</i> and <i>PTPN11</i> Mutations in a <i>FIP1L1-PDGFRA</i>-Positive Myeloproliferative Neoplasm: A Case Report |
| title_sort | therapeutic challenges and emerging strategies for i t674i i and i ptpn11 i mutations in a i fip1l1 pdgfra i positive myeloproliferative neoplasm a case report |
| topic | eosinophilic disorder <i>FIP1L1-PDGFRA T674I</i> mutation imatinib resistance <i>PTPN11</i> mutation myeloproliferative neoplasm |
| url | https://www.mdpi.com/2075-1729/15/3/505 |
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