Ghaith Abu-Zeinah, MD
Assistant Professor of Medicine
Division of Hematology and Oncology
Weill Cornell Medicine
The classical Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs) – essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) – are chronic blood cancers that cause burdensome symptoms1 and increase the risks of thrombosis, bleeding, and evolution to more aggressive malignancies such as acute myeloid leukemia (AML). These complications are associated with shortened survival of patients—as shown by our analysis of the United States (US) National Institutes of Health Surveillance, Epidemiology, and End Results (SEER) cancer database2—but they can be prevented with appropriate treatment3.
MPNs are driven by gene mutations in JAK2, CALR, and MPL, that are acquired in bone marrow stem cells. These mutations augment cellular signaling in hematopoiesis leading to excess production of platelets, white blood cells, and/or red blood cells. A Danish population study showed that JAK2, CALR mutations are more frequent than previously anticipated, being present in 3.2% of the general population4. Although 97.5% of those carrying mutations had no clinical diagnosis of MPN, more than 50% of them develop an MPN 5-10 years later5. This finding is not surprising because mutations originate many years before clinical manifestations6. Accordingly, there is great opportunity for early detection of MPNs yet no screening recommendations.
The diagnosis of MPNs, according to the World Health Organization’s (WHO) 2016 criteria, is made when abnormal blood counts occur in the presence of a driver mutation and characteristic abnormalities of the bone marrow7. A standard approach to treatment of MPNs has been proposed by the European LeukemiaNet (ELN) and the National Comprehensive Cancer Network (NCCN) and are based on prognosis8,9. Patients who are symptomatic and at high risk of thrombosis and disease complications require prompt treatment with antithrombotic agents and cytoreductive agents such as interferon-alpha, hydroxyurea, and JAK inhibitors. Although these treatments are not curative, some can achieve durable remission for many years. Low-risk patients, or high-risk patients with MPNs not responding to standard therapy, may benefit from clinical trials of investigational treatments. Hematopoietic stem cell transplant (HSCT) is a potentially curative option generally reserved for patients who: 1) have more aggressive MPNs likely to cause more harm than HSCT itself, 2) are in reasonably good health, and 3) have an HLA-matched donor.
Raising awareness in MPNs is important because MPN patients suffer burdensome symptoms and potentially fatal complications that can be prevented with treatment3. Additionally, these chronic blood cancers are more common than previously anticipated, and are potentially a public health issue. Early and accurate diagnosis, and appropriate intervention, is most likely to improve long-term outcomes and significantly prolong the survival of MPN patients3.
- Mesa RA, Miller CB, Thyne M, et al. Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey. Cancer. 2017;123(3):449–458.
- Abu-Zeinah K, Saadeh K, Silver RT, Scandura JM, Abu-Zeinah G. Excess mortality in younger patients with myeloproliferative neoplasms. Leuk. Lymphoma. 2022;1–5.
- Abu-Zeinah G, Silver RT, Abu-Zeinah K, Scandura JM. Normal life expectancy for polycythemia vera (PV) patients is possible. Leuk. 2021 362. 2021;36(2):569–572.
- Cordua S, Kjaer L, Skov V, et al. Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population. Blood. 2019;134(5):469–479.
- Cordua S, Kjaer L, Skov V, et al. Early detection of myeloproliferative neoplasms in a Danish general population study. Leuk. 2021 359. 2021;35(9):2706–2709.
- Egeren D Van, Escabi J, Nguyen M, Mullally A. Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms. Cell Stem Cell. 2021;
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.
- Barbui T, Tefferi A, Vannucchi AM, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057–1069.
- Ali H, Bose P, Dunbar A, et al. NCCN Guidelines Version 2.2022 Myeloproliferative Neoplasms. 2022;