# AML1-ETO Regulation via the 3'UTR in t(8;21) Acute Myeloid Leukemia

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $40,258

## Abstract

Summary-Abstract:
 One of the common genetic abnormalities in acute myeloid leukemia (AML) is the translocation
between chromosome 8q22 and chromosome 21q22 [t(8;21)(q22;q22)], which gives rise to the AML1-ETO
(AE) fusion gene. AE is a transcription factor that, when expressed, blocks normal myeloid differentiation and
is critical to t(8;21) leukemogenesis, leading to the proliferation of immature leukemic blast cells. However,
t(8;21) alone is insufficient for leukemia development, which requires additional “hits.” Interestingly, t(8;21)
patient single-cell qPCR data from ourselves and others shows that the AE transcript level is much greater in
both t(8;21)+ leukemic/hematopoietic stem cells at diagnosis vs remission, and in t(8;21)+ leukemic blasts vs
t(8;21)+ differentiated monocytes/granulocytes. These data suggest that increasing AE transcript levels is
important to both blocking differentiation and maintaining t(8;21) leukemia. Additional preliminary data
implicates that post-transcriptional stability, associated with specific cis-elements within the AE 3’ untranslated
region (UTR), is a major contributor to increased AE expression. However, it is unknown which additional
trans-factors interact with the AE 3’UTR cis-elements and enhance AE expression in leukemic cells. Identifying
the molecular mechanisms of post-transcriptional regulation during leukemogenesis may provide valuable
insights into the rational therapeutic drug design for treating related malignancies. This proposal seeks to
determine the post-transcriptional mechanisms controlling the enhanced expression of AE and their
contribution to the initiation and maintenance of t(8;21) leukemia. The stability of mRNA transcripts is primarily
regulated through sequence specific interactions of the 3’UTR with microRNAs (miRNAs) and RNA binding
proteins (RBPs), which are both often dysregulated in cancer. Therefore, the proposed studies aim to test the
hypothesis that dysfunction of certain AE 3’UTR-interacting miRNAs and RBPs contributes to the enhanced AE
expression in t(8;21) leukemic cells. The specific aims are to identify miRNAs and RBPs that target the AE
3’UTR and determine their contribution to AE expression and t(8;21) leukemia.

## Key facts

- **NIH application ID:** 9925747
- **Project number:** 5F31CA228324-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Daniel Thomas Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,258
- **Award type:** 5
- **Project period:** 2018-07-02 → 2021-07-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925747

## Citation

> US National Institutes of Health, RePORTER application 9925747, AML1-ETO Regulation via the 3'UTR in t(8;21) Acute Myeloid Leukemia (5F31CA228324-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9925747. Licensed CC0.

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