# Role of KLHL6 inactivation in mature B-cell malignancies

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $368,288

## Abstract

Project Summary
Mature B-cell neoplasms are the fifth most common neoplasm in both males and females. They arise from B-
cells that have entered germinal centers and display great heterogeneity at the clinical and genetic levels. The
clinical success of proteasome inhibitors, bortezomib, and E3 ubiquitin ligase inhibitors, lenalinomide for the
treatment of multiple myeloma and B-cell lymphomas has made the Ubiquitin pathway a bona fide target for
cancer therapeutics. Thus, defining how novel E3 ligases function at a molecular level and investigating their
role in B-cell malignancies remains a major research imperative in order to develop more specific therapeutic
avenues. KLHL6 is a gene of unknown function that is mutated in mature B-cell malignancies such as chronic
lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma. We have
demonstrated that KLHL6 is an E3 ubiquitin ligase and cancer-associated mutations inactivate its catalytic
activity. The goals of this research proposal are to define the molecular and cellular functions of KLHL6 with
regards substrate degradation and analyze the effects of KLHL6-loss in vivo. Our central hypothesis is that
KLHL6 is novel tumor suppressor that may contribute to the pathogenesis of DLBCL and MM by regulating cell
proliferation, differentiation and survival.

## Key facts

- **NIH application ID:** 9982852
- **Project number:** 5R01CA207513-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Luca Busino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,288
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982852

## Citation

> US National Institutes of Health, RePORTER application 9982852, Role of KLHL6 inactivation in mature B-cell malignancies (5R01CA207513-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982852. Licensed CC0.

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