Editor’s Note: From January 9–11, 2026, the 6th China Hematology Discipline Development Conference (CASH) was successfully held in Tianjin. The meeting brought together leading international and national experts in hematology, focusing on frontier scientific advances and national health priorities, fostering deep academic exchange and shaping future directions of the discipline.

During the conference, Oncology Frontier – Hematology Frontier invited Professor Zhigang Cai from Tianjin Medical University to share latest fundamental research advances in four key areas:

  • Clonal Hematopoiesis (CH)
  • Myelodysplastic Syndromes (MDS)
  • Myeloproliferative Neoplasms (MPN)
  • VEXAS Syndrome

These advances provide new perspectives on the molecular mechanisms and evolutionary trajectories of hematologic diseases, while offering important insights for optimizing clinical diagnostic and therapeutic strategies.

Background

Clonal hematopoiesis (CH), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and VEXAS syndrome are not newly emerging fields. Among them, VEXAS syndrome was first reported at the American Society of Hematology (ASH) Annual Meeting in 2020, and has achieved rapid progress over the past five years. Below is a focused overview of the most significant recent breakthroughs across these four domains.

Advances in Clonal Hematopoiesis (CH)

Systematic research on CH dates back to 2014, with over a decade of development. Current breakthroughs concentrate on three major directions:

1. Continuous Exploration of Driving Factors

Beyond classical drivers such as TET2 and TP53, current studies are exploring serum biomarkers and molecular indicators that may contribute to CH initiation and expansion, providing deeper insight into the foundational biological logic of CH development.

2. Identification of Repressors

From a reverse-regulation perspective, research is now focusing on molecular mechanisms that suppress clonal expansion and evolution. As early as 2018, Professor Cai’s laboratory identified anti-inflammatory molecules capable of blocking CH-driving processes, highlighting potential interventional targets.

3. Early Evolutionary Trajectory Tracking

Using single-cell methylation sequencing, researchers are tracing the earliest evolutionary signals of CH. Even subtle molecular changes are being captured, providing a theoretical foundation for early prevention and intervention strategies.

Advances in Myelodysplastic Syndromes (MDS)

Given the high heterogeneity and complex subtyping of MDS, multi-omics integration has become a dominant research paradigm. By integrating genomics, transcriptomics, epigenomics, and other omics data, researchers can:

  • Achieve refined molecular subtyping of MDS
  • Identify subtype-specific molecular pathways and mutation profiles
  • Clarify disease heterogeneity mechanisms
  • Enable precise risk stratification and individualized therapy

This multi-dimensional framework provides a robust theoretical basis for precision medicine in MDS.

Advances in Myeloproliferative Neoplasms (MPN)

The classical driver genes of MPN remain JAK2, MPL, and CALR. Compared with other areas, MPN research at ASH 2025 was more clinically oriented, with fewer basic science studies.

Current fundamental research focuses on clonal competition and evolutionary dynamics, including:

  • Inter-clonal interactions
  • Selective pressures
  • Evolutionary trajectories

These mechanisms are crucial for optimizing disease monitoring, risk assessment, and timing of intervention, and carry significant translational clinical value.

Advances in VEXAS Syndrome

Professor Cai’s laboratory places special emphasis on basic research in VEXAS syndrome.

From a classification perspective, VEXAS can be:

  • Considered within the broader MDS spectrum, or
  • Studied as an independent disease entity

Approximately 2% of MDS patients harbor UBA1 mutations associated with VEXAS.

Key Breakthroughs

1. Disease Modeling

With advances in gene-editing technologies, human hematopoietic stem cells can now be genetically edited to generate disease models. Professor Cai’s team primarily uses animal models to systematically dissect VEXAS pathogenesis, clarifying the causal relationship between inflammatory phenotypes and hematopoietic abnormalities at the organismal level.

2. UBA1-Centered Mechanistic Research

As a monogenic disease, VEXAS research has a clear mechanistic focus:

  • Beyond the classical UBA1 Met41 mutation, mutations in other functional regions may induce similar pathogenic effects
  • Research is expanding into non-coding regions of the UBA1 gene

All current research converges on comprehensive molecular dissection of UBA1-driven pathogenic mechanisms.

3. Interaction With Other MDS Drivers

The interplay between UBA1 mutations and other common drivers (e.g., TET2, TP53) has become a major research focus. This interaction network is essential for understanding disease progression and has direct clinical relevance.

Clinical Translation

Based on these findings, Professor Cai emphasized that:

UBA1 mutation screening should not be omitted in routine molecular testing of MDS patients.

Moreover, his team plans to promote the inclusion of UBA1 in standardized myeloid malignancy gene panels in 2026, aiming to improve early identification and clinical management of VEXAS syndrome.

Expert Profile

Professor Zhigang Cai

Professor Zhigang Cai Tianjin Medical University

  • Department of Pharmacology, School of Basic Medical Sciences
  • Distinguished Professor, Tianjin Medical University
  • Collaborative PI, Hematology & Rheumatology Departments, Tianjin General Hospital
  • PI, State Key Laboratory of Hematology and Health
  • PI, Tianjin Key Laboratory of Inflammation Biology
  • Scientific Advisor, Beijing Xunyin Biotech Co., Ltd.

Education & Training

  • BSc, Biology, Yunnan University (2001)
  • PhD, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2006)
  • Postdoctoral Fellow & Assistant Professor, Indiana University School of Medicine (2007–2020)

Research Focus

  • Clonal hematopoiesis and hematologic malignancy evolution
  • Molecular regulation of hematopoietic stem cells and immunity
  • Single-cell multi-omics in hematopoietic development and disease

Funding & Publications

  • Principal investigator of multiple National Natural Science Foundation projects (general and key programs)
  • Corresponding author of high-impact publications in Journal of Clinical Investigation (2025), Cell Reports (2025, two papers), Annals of the Rheumatic Diseases (2023), and others
  • 16 high-quality publications in the past 5 years after returning to China
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Last updated on 2026.01.30