Chronic Myelomonocytic Leukemia in the Young (Aged 50 years and Younger): Divergent Clinical and Molecular Characteristics from the Elderly

Authors

• Chi Young Ok, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
• Anuya Natu, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
• Parnaz Daneshpajouhnejad, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
• Lamiaa A. Fathalla, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
• Emily Symes, Department of Pathology, University of Chicago, Chicago, Illinois, USA.
• Paul Barone, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
• Anna Shestakova, Department of Pathology, Associated Regional and University Pathologist (ARUP) Laboratories, University of Utah, Salt Lake City, Utah, USA.
• Kathryn K. Foucar, Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
• Carlos Bueso-Ramos, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
• Guillermo Montalban-Bravo, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
• Attilio Orazi, Department of Pathology, Texas Tech Health Sciences Center, El Paso, Texas, USA.
• Mrinal Patnaik, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
• Robert Hasserjian, Department of Pathology, Massachusetts General Hospital, Massachusetts, Massachusetts, USA.
• Daniel Arber, Department of Pathology, University of Chicago, Chicago, Illinois, USA.
• Julia T. Geyer, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
• Adam Bagg, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
• Kaaren K. Reichard, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
• Sa A. Wang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Document Type

Article

Publication Date

11-15-2025

Abstract

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is largely a disease of individuals older than 50 years; its occurrence in patients aged 50 years and younger is rare. The authors sought to characterize the clinicopathologic features and genetic profile of young-onset (age 50 years and younger) CMML (y-CMML) compared with older onset (older than 50 years) CMML (o-CMML).

METHODS: The authors conducted a multi-institutional study of 32 patients with y-CMML and 119 patients with o-CMML, analyzing clinical, morphologic, cytogenetic, and molecular data.

RESULTS: Patients who had y-CMML frequently presented with splenomegaly (59% vs. 11%; p <  .001) and hepatomegaly (25% vs. 2%; p <  .001) compared with those who had o-CMML. Although the overall incidence of cytogenetic abnormalities was similar, patients who had y-CMML exhibited distinct mutational patterns. PTPN11 mutations were significantly more common in y-CMML (13% vs. 3%; p = .034) than in o-CMML, whereas TET2 (6% vs. 57%; p <  .001) and SRSF2 (16% vs. 46%; p = .002) mutations were significantly less frequent. In addition, multi-hit TET2 (6% vs. 34%; p = .002) and TET2-SRSF2 (3% vs. 29%; p = .003) co-mutations were rare in y-CMML. However, the molecular differences did not affect the CMML-specific risk-stratification categories because the clinical outcomes, including overall survival and leukemia-free survival, did not differ between the two groups.

CONCLUSIONS: CMML in patients aged 50 years and younger is rare and presents with unique clinical and mutational features, suggesting a distinct pathogenesis.

Recommended Citation

Ok CY, Natu A, Daneshpajouhnejad P, Fathalla LA, Symes E, Barone P, Shestakova A, Foucar KK, Bueso-Ramos C, Montalban-Bravo G, Orazi A, Patnaik M, Hasserjian R, Arber D, Geyer JT, Bagg A, Reichard KK, Wang SA. Chronic myelomonocytic leukemia in the young (aged 50 years and younger): Divergent clinical and molecular characteristics from the elderly. Cancer. 2025 Nov 15;131(22):e70176. doi: 10.1002/cncr.70176. Erratum in: Cancer. 2026 Jan 1;132(1):e70232. doi: 10.1002/cncr.70232. PMID: 41236405; PMCID: PMC12617386.