ArticleBlood advances2020
RAS/CBL mutations predict resistance to JAK inhibitors in myelofibrosis and are associated with poor prognostic features.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 77 citations in OpenAlex.
- Survival outcomes and treatment patterns in myelofibrosis in the JAK inhibitor era.British journal of haematology · 2026Article
- Clinical implications of RAS mutations in AML: prognostic significance is based upon the involved gene and mutation complexity.Blood advances · 2026Article
- The Role and Impact of Non-driver Gene Mutations in Myelofibrosis.Current hematologic malignancy reports · 2026Review
- Understanding Triple Negative Myeloproliferative Neoplasms and Identifying Molecular Drivers.Current hematologic malignancy reports · 2026Review
- [External validation and incremental value assessment of the RR6 prognostic model in Chinese myelofibrosis patients treated with ruxolitinib: focusing on overall survival].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- JAK2 inhibition mediates clonal selection of RAS pathway mutations in myeloproliferative neoplasms.Nature communications · 2025Article
- Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.American journal of hematology · 2025Review
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- Pathogenesis and management of high molecular risk myeloproliferative neoplasms.Haematologica · 2025Review
- Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemia.Blood · 2025Article
- JAK Inhibitors for Myelofibrosis: Strengths and Limitations.Current hematologic malignancy reports · 2024Review
- Prognostic and Predictive Models in Myelofibrosis.Current hematologic malignancy reports · 2024Review
- Validation and molecular integration of the RR6 model to predict survival after 6 months of therapy with ruxolitinib.Haematologica · 2024Article
- Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- Upfront allogeneic transplantation versus JAK inhibitor therapy for patients with myelofibrosis: a North American collaborative study.Bone marrow transplantation · 2024Observational
- Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements.Cancers · 2024Review
- CALR mutations possess unique prognostic relevance in myelofibrosis-before and after transplant.Bone marrow transplantation · 2024Article
- Editorial: Biological and clinical implications of the mutational landscape in myeloproliferative neoplasms.Frontiers in oncology · 2024Article
- Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The dysregulation of the JAK/STAT pathway drives the pathogenesis of myelofibrosis (MF). Recently, several JAK inhibitors (JAKis) have been developed for treating MF. Select mutations (MTs) have been associated with impaired outcomes and are currently incorporated in molecularly annotated prognostic models. Mutations of RAS/MAPK pathway genes are frequently reported in cancer and at low frequencies in MF. In this study, we investigated the phenotypic, prognostic, and therapeutic implications of NRASMTs, KRASMTs, and CBLMTs (RAS/CBLMTs) in 464 consecutive MF patients. A total of 59 (12.7%) patients had RAS/CBLMTs: NRASMTs, n = 25 (5.4%); KRASMTs, n = 13 (2.8%); and CBLMTs, n = 26 (5.6%). Patients with RAS/CBLMTs were more likely to present with high-risk clinical and molecular features. RAS/CBLMTs were associated with inferior overall survival compared with patients without MTs and retained significance in a multivariate model, including the Mutation-Enhanced International Prognostic Score System (MIPSS70) risk factors and cytogenetics; however, inclusion of RAS/CBLMTs in molecularly annotated prognostic models did not improve the predictive power of the latter. The 5-year cumulative incidence of leukemic transformation was notably higher in the RAS/CBLMT cohort. Among 61 patients treated with JAKis and observed for a median time of 30 months, the rate of symptoms and spleen response at 6 months was significantly lower in the RAS/CBLMT cohort. Logistic regression analysis disclosed a significant inverse correlation between RAS/CBLMTs and the probability of achieving a symptom or spleen response that was retained in multivariate analysis. In summary, our study showed that RAS/CBLMTs are associated with adverse phenotypic features and survival outcomes and, more important, may predict reduced response to JAKis.
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