December 11, 2023
By Dibash Kumar Das, PhD
In a comprehensive investigation aimed at understanding the prognostic implications of dynamic thrombocytopenia in patients with myelofibrosis (MF), researchers from the Seoul St. Mary's Hematology Hospital have uncovered crucial genetic and immunologic factors associated with this phenomenon. The study findings were presented at the 65th ASH Annual Meeting and Exposition (Abstract 1835).
Myelofibrosis, categorized as a subtype of Philadelphia-negative myeloproliferative neoplasms (MPNs), is typified by an excessive production of mature blood cells. This condition encompasses primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), often emerging from polycythemia vera and essential thrombocythemia. The clinical manifestations of MF include bone marrow fibrosis, anemia, splenomegaly, and various MF-associated symptoms, with some cases exhibiting cytopenic features linked to inferior outcomes.
Past studies assessing the prognostic impact of cytopenia upon diagnosis encountered limitations in reflecting the progression of cytopenia throughout the disease course, according to the authors. Consequently, in the current study, Tong-Yoo Kim and colleagues employed a time-dependent model to explore the prognostic relevance of dynamic thrombocytopenia in patients with MF while delving into associated genetic and immunologic factors.
Analyzing data from 226 MF patients treated at Seoul St. Mary's Hematology Hospital between December 2001 and August 2021, the research integrated DNA samples for next-generation sequencing (NGS) analysis and conducted immunophenotypic analysis through multiparameter flow cytometry to assess immune subsets.
Among the patients, the study delineated three groups based on platelet counts: those with platelet counts of 100 × 109/L or more (PLT ≥100), progression to thrombocytopenia (PROG), and platelet counts less than 100 × 109/L (PLT <100). Notably, patients in the PLT ≥100 group exhibited a higher 4-year overall survival rate compared to those in the PROG and PLT <100 groups (P<0.001). Further analysis using a time-dependent covariate approach revealed that the progression of thrombocytopenia significantly correlated with inferior overall survival (P=0.004). Moreover, ASXL1 and IDH1 mutations were identified as additional factors linked to poor overall survival.
The study also unveiled distinctive immunological features, noting a lower frequency of CD45RA+CD4+ T cells in the PROG group compared to the PLT ≥100 group. Additionally, the detection of ASXL1 mutation was notably higher in the PROG group, indicating a correlation between genomic alteration of ASXL1 and decreased CD45RA+CD4+ T cells.
“This research highlights the prognostic value of dynamic thrombocytopenia in MF patients and identifies genetic alterations and immune cell subsets associated with the progression to thrombocytopenia. Further exploration is warranted to decipher the critical clones and immune microenvironment signatures linked to cytopenic features in MF patients, offering potential avenues for more targeted and effective therapeutic interventions,” concluded study presenter Kim, Assistant Professor in the Department of Hematology at the Yeouido St. Mary’s Hospital College of Medicine in The Catholic University of Korea, Seoul.
Dibash Kumar Das is a contributing writer.