Myelofibrosis

Aspirin sits in a different place in myelofibrosis, or MF, than it does in many other cancer settings.

Here, aspirin already has a recognised role in selected patients because thrombosis risk is a major issue across the myeloproliferative neoplasms, or MPNs. It also makes sense to ask whether aspirin may have broader anti-inflammatory, disease-modifying, or anti-fibrotic relevance in MF itself.

That is the key split in this topic.

Overview

MF is not only a clonal blood cancer.

It is also a disease of platelet activation, cytokine excess, bone-marrow fibrosis, and chronic JAK-STAT pathway signalling.

That makes aspirin biologically interesting for four reasons:

• it suppresses platelet COX-1 and thromboxane A2, or TXA2

• it may reduce NF-κB-driven inflammatory pressure

• salicylate biology intersects with JAK-STAT and TGF-β-linked fibrosis pathways

• MPNs create unusually fast platelet turnover, which changes how aspirin dosing behaves

The strongest current clinical use is still thrombosis prevention.

The broader anti-fibrotic and disease-modifying story is still early.

What the human evidence shows

Why some MF patients already use aspirin

Aspirin is already used in MF mainly to reduce arterial and microvascular thrombotic risk.

There is also growing interest in whether it may matter in other ways.

That logic comes from the wider MPN literature, where thrombotic events remain a major cause of morbidity and mortality. Aspirin works here through irreversible COX-1 acetylation in platelets, which suppresses TXA2 generation and reduces platelet aggregation. Read the Haematologica review

Unlike some solid-tumour aspirin pages, MF is a setting where aspirin may already be used for a standard haematology reason. It still does not suit every MF patient. The balance changes quickly when platelet counts fall, bleeding history appears, or anticoagulation is already in place. Read the Macmillan summary

What recent MF data suggest

A 2025 ASH abstract reported a real-world cohort of 215 consecutive MF patients and found a trend toward lower thrombosis risk in patients receiving aspirin. Read the ASH abstract

True MF-specific aspirin datasets are still rare.

This was not a randomised trial. It does not prove aspirin improves survival or changes marrow fibrosis. It does support the practical view that aspirin remains relevant in MF because the thrombotic question is real.

Why dosing can be different in MPNs

Standard once-daily low-dose aspirin often gives incomplete platelet suppression in MPNs.

The reason is accelerated platelet production. New platelets enter the circulation without aspirin-mediated COX-1 acetylation, which means TXA2 recovery can happen faster than expected. A 2023 study confirmed that immature platelet fraction, or IPF, and residual TXA2 output measured as serum TXB2 are both higher in MPN patients than in controls. Read the open-access paper

That makes MF different from ordinary cardiovascular aspirin use.

In MPN pharmacodynamic studies, including the ARES programme and later follow-up work, 100 mg twice daily suppressed TXA2 more completely than once-daily dosing and improved microvascular symptoms without a major bleeding signal in selected patients. Read the pharmacodynamic paper

Most of this evidence comes from ET and PV, not pure MF cohorts.

So the dosing lesson is probably relevant to MF biology, but much of it still comes from the wider MPN field rather than from large MF-only trials.

Why aspirin may matter beyond clot prevention

JAK-STAT and NF-κB overlap

MF is strongly driven by JAK-STAT pathway activation.

That is usually linked to JAK2, CALR, or MPL-driven signalling, plus a chronic inflammatory state that feeds back on the malignant clone and on stromal cells.

Aspirin becomes interesting here because salicylate-related signalling can suppress both STAT3 phosphorylation and NF-κB activity in model systems. That means aspirin touches two pathways that matter deeply in MF biology. Read the open-access mechanistic paper

Aspirin is not functioning like a true JAK inhibitor.

It does, however, touch some of the same inflammatory wiring.

Cytokine suppression and inflammatory pressure

MF is a cytokine-heavy disease.

High levels of IL-6, TNF-α, TGF-β, and related mediators help drive constitutional symptoms, marrow remodelling, stromal activation, and progressive fibrosis.

Aspirin and salicylates can inhibit IKKβ and downstream NF-κB signalling. That can reduce production of several of these same inflammatory mediators. Read the open-access fibrosis paper

MF is not only about the malignant clone.

It is also about the inflammatory environment the clone creates.

That is one reason aspirin remains mechanistically interesting even though direct MF disease-modification data is still missing.

Anti-fibrotic plausibility

This is one of the most interesting areas.

It is also where the research is thinnest.

Several non-marrow fibrosis models suggest aspirin can reduce fibroblast activation, collagen deposition, and pro-fibrotic signalling through pathways that matter to MF, including:

• MAPK-Erk1/2 and PI3K-AKT-β-catenin suppression. Read the cardiac-fibrosis paper

• ROS and p38 pathway inhibition. Read the study

• modulation of TGF-β-linked fibrosis signalling by salicylate. Read the paper

• reduced stellate-cell activation and lower IL-6 and TNF-α in fibrosis models. Read the open-access paper

Bone-marrow fibrosis is driven by activated stromal and fibroblast-like cells responding to cytokines such as TGF-β, PDGF, and inflammatory stress.

Clinical studies here have not caught up yet.

There is still no clinical trial showing aspirin reverses or meaningfully reduces bone-marrow fibrosis in MF patients. Read the review record

Aspirin-triggered lipoxins

Aspirin may also matter through a more specialised pro-resolution pathway.

When aspirin acetylates COX-2, the pathway can shift toward production of 15-epi-lipoxin A4, often called an aspirin-triggered lipoxin, or ATL. These mediators do not just suppress inflammation. They help actively resolve it. Read the open-access review

MF is not simply an inflamed state. It is a chronically dysregulated inflammatory state that fails to switch off cleanly.

In lung-fibrosis models, aspirin-triggered lipoxin signalling has shown anti-fibrotic and pro-resolution effects. A randomised study in healthy volunteers also found that 81 mg aspirin increased circulating ATL levels while lowering TXB2. Read the open-access review

This pathway has not yet been shown to change outcomes in MF. That may simply reflect how little direct MF research has been done here.

Clinical positioning

What this means in practice

In MF, aspirin already matters clinically, mainly for a haematology reason rather than a direct anti-cancer one.

That is why it helps to keep two ideas separate:

• where aspirin is already useful

• where aspirin is still promising but unproven

Right now:

• aspirin has real value in selected MF patients for thrombosis and microvascular-risk management

• MPN biology creates a genuine aspirin-dosing problem that may make twice-daily plain aspirin more pharmacodynamically rational than once-daily dosing in some patients

• aspirin also has credible JAK-STAT, NF-κB, cytokine, and fibrosis-pathway overlap with MF biology

• there is still no clinical proof that aspirin improves marrow fibrosis, spleen response, symptom burden, or survival through disease modification

Aspirin is already relevant in MF.

The wider disease-modifying story is still early.

If aspirin is being discussed, it helps to be clear about the goal.

Is the aim clot prevention?

Or is the aim to explore whether aspirin might also help with inflammation or fibrosis?

Those are different conversations.

The most useful questions for the haematology team are:

1. Is aspirin being considered because of thrombotic risk, microvascular symptoms, or both?

2. What is the current platelet count, and is there any concern about bleeding, varices, or acquired von Willebrand disease?

3. Is the patient JAK2-mutant, previously thrombosed, or otherwise in a subgroup where aspirin logic is stronger?

4. If aspirin is being used, is the goal simple once-daily prophylaxis, or does accelerated platelet turnover make dosing adequacy a real issue?

5. Are people hoping for anti-fibrotic or disease-modifying benefit that has not actually been shown yet?

The last question matters most.

The anti-fibrotic possibility is still unproven.

References

• Haematologica 2022 review — aspirin, thrombosis, and MPN platelet biology. Read the review

• ASH 2025 abstract — real-world aspirin therapy in 215 consecutive MF patients. Read the abstract

• Long-term MPN aspirin pharmacodynamics — twice-daily versus once-daily low-dose aspirin. Read the paper

• Open-access 2023 paper — residual TXA2 generation, immature platelet fraction, and aspirin non-responsiveness in MPNs. Read the paper

• Open-access mechanistic paper — aspirin effects on STAT3 and NF-κB signalling. Read the paper

• Open-access fibrosis paper — aspirin suppresses TLR4-MyD88-NF-κB, IL-6, and TNF-α in fibrosis models. Read the paper

• Cardiac-fibrosis model — aspirin reduces fibrosis through MAPK-Erk1/2 and PI3K-AKT-β-catenin pathways. Read the paper

• ROS and p38-linked anti-fibrotic paper. Read the study

• Salicylate and TGF-β modulation paper. Read the paper

• Aspirin-triggered lipoxins and pro-resolution signalling. Read the open-access review

• MF background and practical caution summary. Read the Macmillan summary

• Review record on aspirin in MPNs and evidence limits. Read the record

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