Age-related blood mutations can speed or slow breast cancer in mice

As people get older, their blood stem cells pick up mutations. Sometimes a single mutated cell grows into a large family of identical cells, a common change known as clonal hematopoiesis. It becomes more frequent with age and has been tied to worse outcomes in cancer patients, but how it affects solid tumors has stayed unclear.¹ A new preprint tries to answer part of that question in mice, and reports a surprise: two of the most common versions of the change pushed breast tumors in opposite directions.¹

The paper was posted on 12 November 2026 by Gonullu, Zielinska, Fullin, Prisco, Boettcher, Caiado and Manz.¹ It has not been peer reviewed, and all of its results are in animals and cells. Nothing here has been shown in people.¹

What the researchers did

The team used mice engineered so their blood cells carried a mutation in one of two genes: Tet2 or Dnmt3a. These are two of the most common drivers of age-related blood clones.¹ They then gave the mice breast tumors using a standard model that places the tumor where it would naturally grow, and watched what happened as the animals aged.¹

The result split cleanly by mutation. In aged mice, the Dnmt3a mutation prevented breast tumors from progressing, while the Tet2 mutation drove tumors to grow.¹ In other words, two changes that are often lumped together under the same umbrella did not act the same way.

The difference came down to immune cells

When the researchers looked closely, they found the two mutations built very different immune environments inside the tumor.¹

In the Dnmt3a mice, the blood cells that moved into the tumor set up a type of immune cell the authors describe as interferon-driven, so-called tumor-associated macrophages that displayed high levels of a surface marker called MHCII. These cells supported killer T cells, the immune cells that attack tumors, and the tumor was rejected.¹

The Tet2 mice built the opposite. Their tumor macrophages were inflammatory and suppressed the immune system. They made more of two signaling molecules, called IL-1 and CXCL2, showed less of the MHCII marker, and failed to recruit and switch on T cells.¹ The authors describe this as an immunosuppressive state that let the tumor grow.¹

Blocking inflammation slowed the tumors

The team then tried to reverse the harmful version. In the aged Tet2 mice, they used drugs that block the receptors for those two inflammatory signals, named IL-1R1 and CXCR2.¹ Blocking either one reduced tumor progression and partly restored the anti-tumor immune response.¹

The authors frame this as the practical takeaway: inflammation driven by IL-1 and CXCL2 looks like a weak point in the tumor-promoting, Tet2-mutant version, and a possible place for treatment to aim.¹ That is a reasonable next hypothesis, not a proven therapy. The drugs were tested in mice.

What it does not show

Several limits are worth being clear about. This is a mouse study, and mouse tumor models do not always behave the way human cancers do. It is a preprint, so it has not yet been through peer review, where other scientists check the methods and numbers.¹ The work looked at how tumors grew once they were present, not at whether these blood mutations start cancer in the first place.¹

It also does not tell an individual anything about their own risk. Clonal hematopoiesis is extremely common with age, and carrying one of these mutations is not the same as having or being destined to get cancer. The study measured tumor behavior in engineered mice, not outcomes in people.¹

How it fits with other work on these mutations

The same two genes, TET2 and DNMT3A, keep showing up across age-related disease, which makes the opposite-effects finding in cancer stand out. Clonal hematopoiesis is defined by how large the mutated clone grows, and once one of these clones passes a set threshold it is called CHIP; roughly half of CHIP cases are driven by DNMT3A mutations.² Greater expansion of these clones has been linked to a higher risk of cardiovascular disease and blood cancers.² In one set of bone marrow samples collected during heart surgery, researchers detected CHIP in 45 of 191 people, or about 24 percent.²

In the heart, the two mutations have mostly looked harmful together rather than opposed. In studies of calcific aortic valve disease, the most common age-related heart valve disease, these clones promote inflammation, and silencing either TET2 or DNMT3A in immune cells pushed cells toward calcification.³ Those mutations occur in more than 30 percent of patients with severe disease, and patients who carry them have a worse prognosis.³ Against that backdrop, a cancer result in which Tet2 and Dnmt3a pull in opposite directions is a reminder that a blood mutation’s effect can depend heavily on which gene, which organ and what age.¹

The preprint’s own conclusion echoes this: the effects of these blood clones on cancer are mutation- and age-dependent.¹ That nuance is harder to act on than a single rule, but it may be closer to what is actually going on.

What to watch next

The clearest next steps are peer review of this preprint and, eventually, whether the pattern holds in human data rather than mice. The IL-1 and CXCR2 blocking approach is the piece most likely to be followed up, because drugs aimed at those targets already exist for other conditions and could in principle be tested against tumor-promoting clones.¹ For now, the honest summary is narrow: in aged mice, one common blood mutation sped breast tumors and another slowed them, and the authors traced the split to the immune cells those mutations build inside the tumor.¹