# Novel functions of CDK6 in T-cell leukemia progression

> **NIH NIH R37** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $345,413

## Abstract

One of the most common causes of treatment failure in T-cell leukemia is dissemination of malignant cells. The
overarching goal of this proposal is to test whether inhibition of CDK6 kinase holds promise as an effective
therapeutic strategy for treatment of T-cell leukemia dissemination.
Cyclin D3/CDK6 is the major type of cyclin D/CDK in T-cell acute lymphoblastic leukemia (T-ALL), and kinase
activity of CDK6 in T-ALL is dramatically enhanced as its inhibitor proteins are mutated in over 50% of T-ALL
cases. Targeting CDK6 for T-ALL therapy is promising as it prevents leukemia cell proliferation and induces T-
ALL apoptosis. It is not clear whether or how CDK6 regulates T-ALL dissemination. In this study, we will
elucidate the novel regulatory mechanism of cyclin D3/CDK6 in T-cell leukemia dissemination. We
obtained substantial preliminary evidence to show that CDK6 plays an important role in T-ALL dissemination by
regulating nuclear translocation and phosphorylation of PFKP. We also found that CDK6-dependent nuclear
enrichment of PFKP may have a prognostic impact in T-cell lymphoma/leukemia. In the proposed work, we will
extend these findings. In Aim 1, we will examine how cyclin D3/CDK6 regulates PFKP nuclear translocation to
promote leukemia invasion. In Aim 2, we will determine how CDK6 mediated PFKP phosphorylation increases
CXCR4 and PD-L1 expression to enhance leukemia cell dissemination. In Aim 3, we will perform a translational
study to test the prognostic value of nuclear PFKP in T-cell lymphoma/leukemia using an expanded clinically
well-annotated cohort of T cell lymphoma/leukemia patients, and a pre-clinical study of the therapeutic effect of
a CDK6 specific degrader on T-ALL mouse models. The expected overall impact of this proposal is that it may
elucidate the molecular function of CDK6 in T-ALL dissemination, and it may lead to novel targeted therapeutic
strategies based on CDK6 inhibition.

## Key facts

- **NIH application ID:** 10456933
- **Project number:** 5R37CA251165-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Haizhen Wang
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $345,413
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456933

## Citation

> US National Institutes of Health, RePORTER application 10456933, Novel functions of CDK6 in T-cell leukemia progression (5R37CA251165-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456933. Licensed CC0.

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