Triple-negative primary MF: A comparative analysis of phenotype, genotype, and outcomes

A comparative analysis examining phenotype, genotype, and outcomes in patients with triple-negative primary myelofibrosis (MF) – defined by the absence of JAK2, CALR, and MPL mutations – vs JAK2-mutated primary MF was recently published in Blood Cancer Journal by Bashir et al. (N = 760; n = 92 triple-negative primary MF; n = 668 JAK2-mutated primary MF).

Key data: Compared with JAK2-mutated cases, triple-negative primary MF demonstrated lower median hemoglobin levels (9.4 vs 10.7 g/dL; p < 0.01), higher rates of transfusion-dependent (TD) anemia (40 vs 23%; p < 0.01), lower rates of leukocyte count >11 × 10⁹/L (33% vs 45%; p = 0.01), lower median platelet counts (157 vs 243 × 10⁹/L; p < 0.01), and higher rates of severe anemia (47% vs 27%; p < 0.01). Unlike in JAK2-mutated primary MF, unfavorable karyotype is a significant independent predictor of worse overall survival (OS) in triple-negative primary MF (p = 0.65 vs p = 0.02). Specifically, unfavorable karyotype clustered with ASXL1 (62% vs 30%; p = 0.01) and EZH2 (15% vs 0%; p < 0.01) mutations, and negatively impacted OS (median 27 months vs 109 months; p = 0.01).

Key learning: Triple-negative primary MF is not a prognostically distinct subgroup but demonstrates unique clinical features, including more severe cytopenias and differential prognostic karyotype clustering. These findings highlight the importance of comprehensive molecular profiling in primary MF prognostication.