Immature blood cells may be marker of disease severity in myelofibrosis

Circulating myeloblasts (CMB), a type of immature white blood cell commonly found in the bloodstream of people with myelofibrosis, may serve as a marker of disease severity and outcomes, according to a pilot study.

Blood levels of myeloblasts, measured by a sensitive technique called flow cytometry, correlated with established markers of disease severity, the researchers noted. Per the team, such testing revealed meaningful changes in disease activity that were below the thresholds used in conventional microscopy-based assessments.

“A novel method for the evaluation of [CMB count] and [percentage] provides valid biomarkers of disease activity at diagnosis of [myelofibrosis] and also has the potential to recognize natural disease evolution,” the team wrote.

The researchers say “this novel approach for quantifying CMBs has strong potential to reflect disease activity and prognosis in [myelofibrosis].”

The study, “Circulating CD117+/CD34+/CD45dim Myeloblasts as Biomarkers of Disease Activity in Primary Myelofibrosis — A Pilot Study,” was published in the journal eJHaem.

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May 1, 2026 by Marisa Wexler MS

Low blood cell counts before treatment may signal higher risk in myelofibrosis

Myelofibrosis is marked by abnormalities in blood cell production and scarring within the bone marrow. It belongs to a group of chronic blood cancers, called myeloproliferative neoplasms, in which the bone marrow produces too many red blood cells, white blood cells, or platelets. Platelets are tiny cell fragments that help blood to clot.

At the biological level, myelofibrosis is driven by overactivation of the JAK-STAT signaling pathway, caused by mutations in the JAK2, CALR, or MPL genes. Progression to leukemia is the most serious outcome, occurring in approximately 10% to 20% of patients within 10 years of diagnosis.

Available treatments manage symptoms but don’t cure the disease

Available drug treatments, including JAK inhibitors, can help manage symptoms but do not cure the disease, and their effect on overall survival remains limited and debated. The only potentially curative treatment is a stem cell transplant, but this is restricted by significant risks of serious complications.

Because of these treatment limitations, accurately classifying patients by risk level is considered essential for guiding treatment decisions.

One potentially useful marker of disease activity is the level of circulating myeloblasts, or immature white blood cells, known as CMBs for short. These typically are examined under a microscope. Still, this method has drawbacks, including difficulty distinguishing immature cells solely by appearance.

A related measurement, the count of circulating CD34-positive cells, a type of immature blood cell identified by a surface protein CD34, has shown promise in several studies as a marker for distinguishing myelofibrosis from other myeloproliferative neoplasms and for predicting survival.

In this study, researchers used flow cytometry to measure circulating levels of CMBs expressing the proteins CD34, CD117, and CD45 at lower levels, specifically corresponding to blood myeloblasts (CMB-FC).

A total of 29 people with myelofibrosis, ages 32 to 85, were involved in the study. Of them, 45% had prefibrotic myelofibrosis, representing a milder, earlier stage. The rest had overt disease, a more advanced, symptomatic phase. The mean CMB-FC relative percentage (CMB-FC%) was 0.28%, below the 1%-2% thresholds used in traditional microscopy-based assessments.

CMB levels also linked to disease’s underlying biology

CMB-FC% was significantly higher in patients with anemia, or low red blood cell counts, than in those without that condition. It was also elevated in patients who required blood transfusions. A high CMB-FC% was associated with low platelet and hemoglobin levels; hemoglobin is the protein in red blood cells that carries oxygen and serves as a marker for red blood cells.

Several markers of the disease’s underlying biology were also associated with CMB-FC levels. A higher proportion of blood cells harboring the JAK2 mutation correlated with a greater number of CMB-FCs. Patients with overt myelofibrosis had higher CMB-FC count and percentage than those with prefibrotic myelofibrosis. CMB-FC count also rose progressively with increasing grades of bone marrow fibrosis, or scarring.

In clinical assessments, higher CMB-FC counts and percentages were associated with worse functional status, as indicated by the Eastern Cooperative Oncology Group (ECOG) Performance Status scores, a scale that measures how disease affects a patient’s ability to function in daily life. CMB-FC% also increased significantly across higher-risk categories in outcome-scoring systems.

Although pretreatment levels varied widely between patients, the researchers found no significant change in CMB-FC count or percentage over the course of treatment.

Because no disease progression events occurred in the main study group during the follow-up period, the team separately examined two patients who were not included in the main cohort but who did experience disease progression.

In the first case, a patient who progressed to leukemia showed a steady rise in CMB-FC count from 8.4 to 574 cells per microlitre over 11 months, with symptoms appearing only at the final time point. In the second case, a patient with worsening disease showed an increase in CMB-FC% from 0.004% to 0.4% over 17 months, which preceded clinical deterioration.

In both cases, these increases occurred while CMB-FC% remained below the 1% cut-off used in standard microscopy-based assessments.

“We recommend retrospectively investigating CMB-FC [counts] and CMB-FC% in other centres to further evaluate their prognostic potential, incorporate them into currently used prognostic scores, and prospectively investigate them as surrogate markers for efficacy and disease progression in clinical trials for the treatment of [myelofibrosis],” the researchers concluded.