Evidence map›Paper›PMID 35331314›Full record

ReviewJournal of hematology & oncology2022

Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias.

Yan Yi, Shenglei Ge

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

Review in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
5.1field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 67 citations in OpenAlex.

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  18. Discovery of the first-in-class DOT1L PROTAC degrader.European journal of medicinal chemistry · 2025
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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

2 authors at 2 institutions in 1 country.

Yan YiDepartments of Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
Shenglei GeDepartments of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Street, Changsha, 410011, Hunan, People's Republic of China. shengleige@csu.edu.cn.
Central South University · CNSecond Xiangya Hospital of Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Disrupting the methylation of telomeric silencing 1-like (DOT1L)-mediated histone H3 lysine 79 has been implicated in MLL fusion-mediated leukemogenesis. Recently, DOT1L has become an attractive therapeutic target for MLL-rearranged leukemias. Rigorous studies have been performed, and much progress has been achieved. Moreover, one DOT1L inhibitor, EPZ-5676, has entered clinical trials, but its clinical activity is modest. Here, we review the recent advances and future trends of various therapeutic strategies against DOT1L for MLL-rearranged leukemias, including DOT1L enzymatic activity inhibitors, DOT1L degraders, protein-protein interaction (PPI) inhibitors, and combinatorial interventions. In addition, the limitations, challenges, and prospects of these therapeutic strategies are discussed. In summary, we present a general overview of DOT1L as a target in MLL-rearranged leukemias to provide valuable guidance for DOT1L-associated drug development in the future. Although a variety of DOT1L enzymatic inhibitors have been identified, most of them require further optimization. Recent advances in the development of small molecule degraders, including heterobifunctional degraders and molecular glues, provide valuable insights and references for DOT1L degraders. However, drug R&D strategies and platforms need to be developed and preclinical experiments need to be performed with the purpose of blocking DOT1L-associated PPIs. DOT1L epigenetic-based combination therapy is worth considering and exploring, but the therapy should be based on a thorough understanding of the regulatory mechanism of DOT1L epigenetic modifications.

Indexed as

HistonesLeukemiaHistone-Lysine N-MethyltransferaseHumansLysineMethyltransferasesMyeloid-Lymphoid Leukemia ProteinDOT1L protein, humanHistone-Lysine N-MethyltransferaseHistonesLysineMethyltransferasesMyeloid-Lymphoid Leukemia ProteinCombined modality therapyDOT1LDrug discoveryEpigeneticsHistone modificationsMLL-rearranged leukemiaProtein–protein interactionsSmall molecule inhibitorsTargeted protein degradation

Identifiers

PMID35331314
PMCPMC8944089
OpenAlexW4220792557

What OpenQuestion holds

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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.