Incorporation of Genomic Determinants Improves Diagnostic Accuracy of Oligomonocytic Chronic Myelomonocytic Leukemia
Recent updates to monocyte count thresholds recognize oligomonocytic chronic myelomonocytic leukemia (OM-CMML) as an early form of CMML. However, the clinical validity of these changes remains uncertain without incorporating biological and genomic factors. In this study, we analyzed a cohort of 911 patients (249 with OM-CMML, 359 with overt CMML, and 303 with myelodysplastic syndromes) using unsupervised clustering to evaluate the role of genomic determinants in refining CMML diagnosis. Our findings show that CMML molecular signatures (biallelic TET2 mutations or SRSF2-TET2 co-mutations) are linked to a distinct transcriptome, monocytic bias, classical monocytosis, and higher risk of progression to overt CMML in OM-CMML cases. We developed a weighted genomic model and diagnostic workflow showing that combining genomic signatures with bone marrow monocyte frequencies in OM-CMML more accurately predicts progression to overt CMML. These findings support integrating genomic determinants, and our clinic-ready diagnostic workflow, into the CMML diagnostic framework to improve accuracy.
Authors
- Alex Bataller
- K. Chien
- Aref Al‐Kali (ORCID: https://orcid.org/0000-0002-0824-3715)
- Xavier Calvo (ORCID: https://orcid.org/0000-0001-7934-9130)
- Yue Wei
- Ziyi Li (ORCID: https://orcid.org/0009-0004-6181-0223)
- Clifford Michael Csizmar (ORCID: https://orcid.org/0000-0002-1221-8854)
- Ian Bouligny (ORCID: https://orcid.org/0000-0002-4274-4249)
- Alexandre Bazinet (ORCID: https://orcid.org/0000-0001-5538-4943)
- Chong Wu (ORCID: https://orcid.org/0000-0002-9593-293X)
- Mrinal M. Patnaik (ORCID: https://orcid.org/0000-0001-6998-662X)
- Christy M. Finke (ORCID: https://orcid.org/0009-0006-2843-9025)
- Mark E. Gurney (ORCID: https://orcid.org/0000-0002-7062-2644)
- David Román (ORCID: https://orcid.org/0000-0003-4980-5064)
- Juan Jose Rodriguez-Sevilla
- Danielle E. Hammond
- Keyur P. Patel
- Nicholas J. Short
- Hagop M. Kantarjian
- L. Jeffrey Medeiros
- Courtney D. DiNardo
- Naseema Gangat
- Hassan Alkhateeb
- Guilin Tang
- Anuya Natu
- Naveen Pemmaraju
- Terra L. Lasho
- Ayalew Tefferi
- Gautam Borthakur
- Guillermo Garcia-Manero
- Farhad Ravandi
- Naval Daver
- Sanam Loghavi
- Guillermo Montalban-Bravo
- Sa A. Wang
- Ghayas C. Issa
- Leonor Arenillas
- Tapan M. Kadia
- Abhishek A. Mangaonkar
- Elias Jabbour
Institutions
- Mayo Clinic (US)
- The University of Texas MD Anderson Cancer Center (US)
- Hospital Clínic de Barcelona (ES)
- Mayo Clinic in Arizona (US)
- Hospital Del Mar (ES)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-01-26
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0264
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00