Hematopathology Expert Series
The Broad-Ranging Impact of Clonal Hematopoiesis: From Diagnostic Considerations to Clinical Implications

Premalignant clonal hematopoiesis refers to a heterogeneous group of conditions, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). CCUS is defined by expansion of a population of hematopoietic cells derived from a single clone, as demonstrated by the detection of myeloid neoplasm-associated somatic mutation or cytogenetic aberration (i.e., clonal hematopoiesis) in association with sustained cytopenia otherwise clinically unexplained and absence of dysplasia. CHIP is a closely related entity defined by the presence of clonal hematopoiesis in the absence of cytopenia. In both conditions, diagnostic criteria of myelodysplastic or other hematologic neoplasm are unmet. The natural history and risk of progression from clonal hematopoiesis to overt malignancy is augmented by mutational dynamics. Substantial data links CHIP to increased all-cause mortality primarily attributable to cardiovascular disease such as myocardial infarction, ischemic stroke, and venous thrombosis. The principal feature underlying these nonhematologic disease associations is a proinflammatory state. Clinical management of patients with clonal hematopoiesis is an area of active investigation.

Originally presented on October 3, 2024, in Salt Lake City, Utah.

Presenter

Jay L. Patel, MD, MBA Professor University of Utah School of Medicine Vice President, PharmaDx and Clinical Trials ARUP Laboratories

Dr. Jay L. Patel is vice president of PharmaDx and Clinical Trials at ARUP Laboratories and professor of Pathology at the University of Utah School of Medicine. Dr. Patel obtained his medical degree from the University of Arizona. Following medical school, he completed an anatomic and clinical pathology residency at the University of Utah and a hematopathology fellowship at Stanford University. Dr. Patel is board certified in anatomic and clinical pathology and hematopathology. He then received a master’s degree in business administration from the University of Utah. Dr. Patel’s clinical and research interests include the application of massively parallel sequencing technologies in hematological malignancies.

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Host

Madhu P. Menon, MD, PhD Associate Professor University of Utah School of Medicine Head of Clinical Operations for Hematopathology ARUP Laboratories

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Panelists

Afaf E. Osman, MD Assistant Professor University of Utah School of Medicine, Huntsman Cancer Institute

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Anton Rets, MD, PhD Associate Professor University of Utah School of Medicine Medical Director, Hematopathology ARUP Laboratories

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Objectives

After this presentation, participants will be able to:

• Summarize the molecular genetic basis of premalignant clonal hematopoiesis
• Apply data-driven diagnostic concepts to distinguish patients with bona fide hematologic malignancy from individuals with clonal hematopoiesis
• Describe the range of clinical implications associated with these precursor conditions and discuss emerging approaches to management

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories