# Advances in the Diagnosis and Treatment of Myeloproliferative Neoplasms (MPNs)

## TL;DR

This paper reviews recent progress in diagnosing and treating myeloproliferative neoplasms, focusing on molecular diagnostics and targeted therapies.

## Contribution

The paper highlights novel diagnostic markers and emerging treatment strategies, including epigenetic and immunotherapy approaches.

## Key findings

- Molecular diagnostics now detect key mutations like JAK2 V617F, CALR, and MPL, improving diagnostic accuracy.
- JAK inhibitors like ruxolitinib are standard treatments, but new strategies targeting epigenetics and the immune microenvironment are emerging.
- Combination therapies and mutation-independent immunotherapies are being explored to overcome drug resistance.

## Abstract

Myeloproliferative neoplasms are rare blood disorders caused by genetic mutations that lead to uncontrolled production of blood cells, increasing risks of blood clots and other complications. Recent advances in molecular diagnostics have transformed diagnosis through identifying key mutations. Treatment now focuses on targeted therapies to reduce symptoms, prevent complications, and improve quality of life. We summarize the latest advancements in the diagnosis and treatment of myeloproliferative neoplasms, highlighting the importance of molecular mechanisms in guiding therapeutic approaches and the potential for precision medicine in the future.

Myeloproliferative neoplasms (MPNs) encompass three principal subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These hematologic malignancies originate from clonal hematopoietic stem cells (HSCs) and exhibit pathological overproduction of myeloid lineage cells. Recent advances in molecular diagnostics, particularly the precise detection of core driver mutations (JAK2 V617F, CALR, and MPL) and non-driver mutations (ASXL1, TET2, SRSF2), has refined diagnostic precision and risk stratification. A variety of prognostic models for MPNs provide guidance for treatment. Treatment methods mainly include bloodletting therapy, low-dose aspirin anticoagulant therapy, cytoreductive therapy, and allogeneic hematopoietic stem cell transplantation (HSCT). JAK inhibitors (such as ruxolitinib) remain the basic therapeutic drugs. However, emerging strategies targeting epigenetic dysregulation and the interaction in the immune microenvironment (such as interferon-α) show promise in reducing drug resistance. New methods, including combination therapy (combination of JAK inhibitors and BCL-XL inhibitors) and mutation-independent immunotherapy, are under investigation. This review summarizes the latest advancements in the diagnosis and treatment of MPNs, highlighting the importance of molecular mechanisms in guiding therapeutic approaches and the potential for precision medicine in the future.