Atypical chronic myeloid leukemia (aCML)

aCML is a rare blood cancer that starts in blood-forming stem cells in the bone marrow. It belongs to a group called myelodysplastic/myeloproliferative neoplasms (MDS/MPN). These diseases have two sides at once. The marrow makes too many of some cells, as in a myeloproliferative neoplasm. But the cells it makes are misshapen (dysplastic), as in a myelodysplastic syndrome.

In aCML, the extra cells are neutrophils and the younger cells that grow into them. The white count is at least 13,000 per microliter of blood. At least 10 in every 100 white cells are young neutrophil forms that are not usually found in the blood.

In 2022, the World Health Organization (WHO) renamed it MDS/MPN with neutrophilia. The new name makes clear that it is not chronic myeloid leukemia (CML). CML is driven by the Philadelphia chromosome and its BCR::ABL1 gene, and aCML never has them. Another system, the International Consensus Classification (ICC), still uses the name atypical CML.

aCML is caused by changes (mutations) in genes inside blood-forming cells. Gene changes are found in more than 9 in 10 people, and many people have several. The most common are in genes called ASXL1, SETBP1, SRSF2, TET2 and EZH2. Less often, genes such as NRAS, CBL, CSF3R, JAK2 and ETNK1 are involved.

These are acquired (somatic) changes. They build up in blood-forming cells during life rather than being present from birth. Changes in chromosomes, such as an extra copy of chromosome 8, are found in about 20 to 40 in 100 people. No single gene or chromosome change is specific to aCML.

Some of these genes matter for research into new treatments. CSF3R changes switch on a signaling pathway that JAK inhibitor medicines can block. NRAS and KRAS changes switch on a different pathway that MEK inhibitor medicines target.

Many people have a large spleen. The National Cancer Institute (NCI) says the spleen is enlarged in about 75 in 100 people. A large spleen can cause a feeling of fullness in the belly. Some people also have general symptoms of feeling unwell.

Anemia (too few red cells) is common and can cause tiredness. Up to a third of people already need blood transfusions when they are diagnosed. The platelet count may be low, which can lead to bleeding, or in some people high.

Among the overlap blood cancers (MDS/MPN), aCML generally has the poorest outlook. In about 30 to 40 in 100 people, it turns into acute myeloid leukemia (AML), often within 12 to 18 months of diagnosis. Other serious problems include white counts that are hard to control, a very large liver and spleen, bleeding and infection.

It often starts with a blood count that shows a high white count. A blood specialist (hematologist) then looks at the cells under a microscope. In aCML, the white count is at least 13,000 per microliter. At least 10 in 100 white cells are young neutrophil forms (promyelocytes, myelocytes and metamyelocytes), and the neutrophils look abnormal (dysplastic). Monocytes make up fewer than 10 in 100 white cells.

A bone marrow biopsy usually shows a very full (hypercellular) marrow crowded with abnormal neutrophil-making cells. Blasts, the most immature cells, are fewer than 20 in 100. Chromosome and gene tests are key. They must show no BCR::ABL1 gene, which rules out CML, and no tyrosine kinase gene fusions such as those involving PDGFRA, PDGFRB or FGFR1. Gene panels often find SETBP1, ASXL1 or ETNK1 changes, which support the diagnosis.

The team also rules out look-alike conditions, such as chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemia and primary myelofibrosis. No single gene test proves aCML, so the diagnosis rests mainly on the blood and marrow picture as a whole.

There is no standard treatment, because aCML is so rare. Care teams often start with hydroxyurea, a pill that can bring the white count down. The effect usually does not last. Azacitidine or decitabine (hypomethylating medicines) may be used, especially while a transplant is being planned or for people who cannot have one. Interferon has helped a few people in small reports, although the NCI summary says aCML responds poorly to it.

Targeted medicines are being studied. Ruxolitinib, a JAK inhibitor, has been tested. In a trial of 44 people, those with a CSF3R change called T618I were more likely to respond. Of the 23 people with aCML in that trial, 2 had a partial response. In the US, ruxolitinib is approved for myelofibrosis, polycythemia vera and graft-versus-host disease, not for aCML. As of September 2026, US trials are recruiting people with MDS/MPN overlap diseases, including aCML, to test new drugs and combinations.

A donor (allogeneic) stem cell transplant is the only treatment that can potentially cure aCML. It uses strong treatment (conditioning) and then healthy blood-forming cells from a donor. In a Dutch national study of 347 people, a transplant was the only treatment linked with longer survival. European transplant experts (EBMT, 2025) recommend finding people who could have a transplant early.

Life with aCML often means frequent blood counts and pills to control the white count. Many people also need transfusions for anemia. Because the disease can change quickly, care teams watch closely for signs that it is turning into acute leukemia.

The diagnosis itself can take time. aCML looks like several other blood cancers, so a bone marrow biopsy and gene tests are needed before the name is settled. Because there is no standard treatment, expert reviews recommend clinical trials whenever possible.

For people who have a transplant, there may be weeks of staying in or near the hospital. After a donor transplant, the immune system takes 1 to 2 years to fully recover. The team watches for infection, graft-versus-host disease and any sign that the leukemia has come back.

A donor transplant for aCML uses healthy blood-forming cells from another person. A European study looked at 42 people transplanted between 1997 and 2006. About two in three donors were brothers or sisters with a matching tissue type (HLA). About one in three were matched unrelated volunteers. In that study, people with an unrelated donor were more likely to be alive without the leukemia coming back. Deaths from other causes were similar.

A later study reports a wider range of donors. A national study in Japan looked at 74 people transplanted between 2003 and 2021. Nearly half of the transplants used an unrelated marrow or blood donor, and about a quarter used donated cord blood. Survival did not differ much between unrelated adult donors and cord blood.

A 2026 expert review notes that transplant use is limited by age, other illnesses and whether a suitable donor can be found. When no family member matches, a registry volunteer or a cord blood unit can make a transplant possible.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

aCML is a serious leukemia. A 2024 expert review puts the typical (median) survival at about 12 to 20 months. In about 30 to 40 in 100 people, it turns into acute myeloid leukemia. Most people are diagnosed after age 65, and older age is linked with shorter survival.

Blood counts and genes matter too. A Mayo Clinic model gives one point each for age over 67, hemoglobin below 10 g/dL and a TET2 gene change. In that small study of 25 people, those with 2 or more points had a median survival of 7 months. Those with 0 or 1 point had 18 months. Medicines such as hydroxyurea can control counts, but experts say none of them change the course of the disease.

A donor transplant is the one treatment linked with longer survival. In the Dutch national study, survival among people who had a transplant leveled off after about 2 years. The authors say this suggests long-lasting remissions or cure in some people. Those who had transplants were younger and fitter, so their results describe a selected group. No figure can say what will happen to one person.