MPN-010: Uncommon cases of concomitant mutations in myeloproliferative neoplasms: A case series

Authors

• Zeeshan Ahmed, Aga Khan UniversityFollow
• Hareem Alam, Aga Khan UniversityFollow
• Noman Ali, Aga Khan UniversityFollow
• Muhammad Shariq Shaikh, Aga Khan UniversityFollow
• Hassan Hayat, Aga Khan University

Document Type

Article

Department

Pathology and Laboratory Medicine

Abstract

Background: Myeloproliferative neoplasms (MPNs) are a diverse group of disorders caused by clonal proliferation of one or more mature myeloid cell lineages. Among the most common Philadelphia-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis, which are primarily driven by mutations in JAK2, CALR, and MPL genes. Although these mutations typically occur exclusively, rare cases have been reported in which two or more coexist in the same patient. Here, we present three uncommon cases of concomitant mutations in MPNs.
Methods:DNA was extracted from patients’ peripheral blood using the QIAamp Blood Mini Kit. Extracted DNAwas subjected to multiplex ligand probe amplification using targeted oligoclonal probes for JAK2 V617F, JAK2 exon 12, MPL, CALR, and c-KIT. The amplified products were analyzed using an Applied Biosystems (ABI 3500) genetic analyzer. The results were interpreted with Coffalyser Analysis Software (MRC Holland).
Results:Our first case involved a 74-year-old female with persistent thrombocytosis (platelet count: 1,070 × 10⁹/L) who presented with microcytic anemia and splenic infarcts. Genetic analysis revealed dual MPL mutations (MPL p. W515K, MPL p.W515L). She was managed for essential thrombocythemia. Despite treatment with hydroxycarbamide, thrombocytosis persisted and she succumbed to urosepsis within 6 months. Another patient with a similar mutation profile but different clinical presentation was a 76-year-old male who presented with anemia and splenomegaly, requiring blood transfusions. Bone marrow biopsy suggested myelofibrosis. Genetic analysis detected MPL p.W515K and MPL p.W515L mutations. He was started on ruxolitinib, leading to clinical improvement with reduced splenomegaly and stable hemoglobin levels and eliminating the need for transfusions over the past year. The third case was of a 58-year-old male with a history of unprovoked portal vein thrombosis who developed progressive anemia, leukocytosis, and symptomatic splenomegaly. Bone marrow biopsy findings suggested myelofibrosis. Genetic testing identified JAK2 p.E543_D544del (exon 12) and MPL p.W515K mutations. He was initiated on ruxolitinib but later showed signs of disease progression with increased circulating blast cells, warranting further evaluation.
Conclusion:Concomitant mutations in Philadelphia-negative MPNs are an uncommon finding, and their clinical implications remain largely unestablished. With limited data available, further studies are required to better understand their clinical significance and potential implications on prognosis and treatment strategies.

Comments

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Publication (Name of Journal)

Clinical Lymphoma Myeloma and Leukemia

DOI

10.1016/S2152-2650(25)02085-3

Recommended Citation

Ahmed, Z., Alam, H., Ali, N., Shaikh, M. S., Hayat, H. (2025). MPN-010: Uncommon cases of concomitant mutations in myeloproliferative neoplasms: A case series. Clinical Lymphoma Myeloma and Leukemia, 25(1).
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1721