Evidence map›Paper›PMID 38053201›Full record

ArticleBiomarker research2023

Repressing HIF-1α-induced HDAC9 contributes to the synergistic effect of venetoclax and MENIN inhibitor in KMT2Ar AML.

Qing Ling, Yutong Zhou, Yu Qian, Jiejing Qian, Yi Zhang, Jinghan Wang, Yanan Zhu, Yile Zhou, Juying Wei, Chunmei Yang and 4 more

Open access · goldAbstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomarker research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Menin in Cancer.Genes · 2024
    Review
  6. International journal of molecular sciences · 2024
    Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Qing Ling *Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Yutong Zhou *Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Yu Qian *Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Jiejing QianDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Yi ZhangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Jinghan WangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Yanan ZhuDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Yile ZhouDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Juying WeiDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Chunmei YangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Jie SunDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China.
Wenjuan YuDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China. drwjyu1977@zju.edu.cn.
Jie JinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China. jiej0503@zju.edu.cn.
Xiang ZhangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, 310003, Zhejiang, China. hillhardaway@zju.edu.cn.
Zhejiang University · CNZhejiang Cancer Hospital · CNZhejiang University Medical College Affiliated Stomatological Hospital · CNFirst Affiliated Hospital Zhejiang University · CN

Funding

Key Research and Development Program of Zhejiang Province 2021C03123National Natural Science Foundation of China 81800199National Natural Science Foundation of China 82170144National Natural Science Foundation of China 82300174Natural Science Foundation of Zhejiang Province LQ20H080001Natural Science Foundation of Zhejiang Province LY21H080003
6 · The paper itself

Abstract

KMT2A-rearranged acute myeloid leukemia (KMT2Ar-AML) is an aggressive subtype of AML with poor response and prognosis. KMT2Ar-AML has been demonstrated to be sensitive to BCL2 inhibitor venetoclax (VEN), but these patients are unable to benefit from current VEN-based regimen (VEN plus azacitidine or low dose-cytarabine), so a novel and KMT2A rearrangement-specific targeting partner is required, and MENIN inhibitor (MEN1i) is a promising one. Herein, we investigated the effect and mechanism of VEN plus MEN1i in KMT2Ar-AML. Our results showed that VEN and MEN1i exhibited a striking synergistic effect in KMT2Ar-AML cell lines (in vitro), primary KMT2Ar-AML cells (ex vivo), and MOLM13 xenotransplantation model (in vivo). Furthermore, we found that VEN plus MEN1i significantly enhanced apoptotic induction in KMT2Ar-AML cell lines. VEN or MEN1i monotherapy disrupted balance of BCL-2/BCL-XL or down-regulated HOXA9/MEIS1, respectively, but these mechanisms were not further strengthened by their combination. RNA-Sequencing identified that HDAC9 was specifically repressed by VEN plus MEN1i rather than monotherapy. We demonstrated that HDAC9 was indispensable for KMT2Ar-AML proliferation and its repression contributed to proliferation inhibition of VEN plus MEN1i. Moreover, we found that hypoxia induced HDAC9 expression in KMT2Ar-AML, and VEN plus MEN1i inhibited hypoxia pathway, especially HIF-1A, and its target HDAC9. As our results indicated, VEN plus MEN1i-mediated HDAC9 down-regulation was partially dependent on HIF-1A repression in KMT2Ar-AML. Hypoxia induction sensitized KMT2Ar-AML to VEN plus MI-503-mediated proliferation inhibition and apoptosis induction. Therefore, repressing HIF-1A-induced HDAC9 contributed to the synergistic effect of VEN and MEN1i in KMT2Ar-AML.

Indexed as

Acute myeloid leukemiaHIF-1A-induced HDAC9KMT2A rearrangementMENIN inhibitorVenetoclax

Identifiers

PMID38053201
PMCPMC10696732
OpenAlexW4389337637

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.