Project Term
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Project Summary
This collaborative program investigates why Hairy Cell Leukemia (HCL) and its variant often relapse despite effective therapies and why bone-marrow fibrosis frequently persists after treatment. This proposal examines fibrosis as both a biomarker and a biological driver of disease. Project 1 determines whether persistent scarring predicts relapse and uses human bone-marrow organoid cultures to test how leukemia and stromal cells interact. Together, these studies connect patient data and experimental systems to reveal how fibrosis contributes to disease persistence in HCL and HCL-v.
Lay Abstract
Hairy Cell Leukemia (HCL) and its variant (HCL-v) form rare blood cancers that respond well to targeted therapy but often relapse years later. A striking and unresolved feature of both diseases is the presence of bone-marrow fibrosis—scarring that can persist even after successful treatment. For many patients, this fibrosis damages normal blood cell production and may signal that leukemia or mutant stem cells remain active. Despite decades of study, the biological cause and clinical meaning of this scarring are still unknown.
This collaborative program brings together investigators at The Ohio State University Comprehensive Cancer Center (OSUCCC–James) and Stanford University to define how fibrosis develops, whether it predicts relapse, and how targeting fibrotic mechanisms can be used to improve patient care. The program addresses this question from clinical, molecular, and experimental perspectives.
Project 1 tests whether persistent fibrosis after therapy serves as a biomarker for relapse. With access to detailed clinical and histologic data from more than 150 patients, researchers will correlate fibrosis severity with genetic mutations in BRAF and MAPK pathways. In addition, they will perform functional experiments in human bone-marrow organoid cultures that reproduce the leukemic environment in the laboratory, allowing direct testing of how residual malignant and stromal cells interact to promote fibrosis.
Together, the project represents an effort to link clinical observation with mechanistic understanding of the contribution of fibrotic processes. By combining patient-derived samples and functional modeling, this program will define how fibrosis contributes to disease persistence in HCL and HCL-v. The results will identify fibrosis as a clinically actionable biomarker.
The Hairy Cell Leukemia Foundation (HCLF) and Blood Cancer United have joined forces to create the Hairy Cell Leukemia Research Initiative program to support targeted research to build a more comprehensive foundational understanding of the molecular basis of hairy cell leukemia (HCL), develop additional therapies, and optimize outcomes for patients with this disease.
Program
