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Last update 08 May 2025

BMI1

Last update 08 May 2025

Basic Info

Synonyms

B lymphoma Mo-MLV insertion region 1 homolog (mouse), BMI1, BMI1 proto-oncogene, polycomb ring finger

+ [6]

Introduction

Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:15386022, PubMed:16359901, PubMed:16714294, PubMed:21772249, PubMed:25355358, PubMed:26151332, PubMed:27827373). The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (PubMed:21772249, PubMed:25355358). In the PRC1-like complex, regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2 (PubMed:15386022, PubMed:21772249, PubMed:26151332).

Drugs associated with BMI1

Unesbulin

Target

BMI1

Mechanism

BMI1 inhibitors

Active Org.

PTC Therapeutics, Inc.

Originator Org.

PTC Therapeutics, Inc.

Active Indication

Diffuse Intrinsic Pontine Glioma [+2]

Inactive Indication

Advanced Malignant Solid Neoplasm [+1]

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

RU-A15

Target

BMI1

Mechanism

BMI1 inhibitors

Active Org.

Rutgers State University of New Jersey

Originator Org.

Rutgers State University of New Jersey

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PTC-209

Target

BMI1

Mechanism

BMI1 inhibitors

Active Org.

Jiangsu Provincial People's Hospital

Originator Org.

University Health Network [+2]

Active Indication

Rheumatoid Arthritis

Inactive Indication

Colorectal Cancer

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with BMI1

NCT05269355

/ TerminatedPhase 2/3

A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma

This study will compare the efficacy and safety of unesbulin plus dacarbazine versus placebo plus dacarbazine in participants with unresectable or metastatic, relapsed or refractory LMS who have received at least 1 prior line of systemic therapy.

Start Date23 May 2022

Sponsor / Collaborator

PTC Therapeutics, Inc.

NCT03761095

/ CompletedPhase 1

A Phase 1B Study of Unesbulin (PTC596) in Combination With Dacarbazine in Patients With Locally Recurrent, Unresectable or Metastatic Relapsed/Refractory Leiomyosarcoma

The primary objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine.
This study will employ the time-to-event continual reassessment method (TITE-CRM) for dose finding. Treatment will be initiated at dose level 2 (DL2) (Dacarbazine 1000 milligrams per square meter [mg/m^2] intravenously [IV] every 21 days in combination with unesbulin 200 milligrams [mg] orally twice weekly) for the first participant. This dose level represents the investigator's best assessment of the MTD based on available toxicity data for both agents. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose-limiting toxicity (DLT) information from all participants previously treated. To enroll additional participants at the RP2D, the study is amended to include an expansion cohort of up to 12 participants (some of whom could be ongoing participants who reconsent).
Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

Start Date13 Mar 2019

Sponsor / Collaborator

PTC Therapeutics, Inc.

NCT03605550

/ Active, not recruitingPhase 1IIT

A Phase 1b Study of PTC596 in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma

The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG).
The main aims of the study are to:
* Find the safe dose of the study drug PTC596that can be given without causing serious side effects.
* Find out the amount of drug that enters blood (in all patients) and tumor (in patients who receive drug prior to a planned surgery for removal of their brain tumor)
During the first cycle (6-7weeks), patients will receive drug orally twice a week in combination with daily RT. During subsequent cycles (4 weeks each), they will receive only the study drug orally twice a week.
Funding Source - FDA OOPD

Start Date01 Aug 2018

Sponsor / Collaborator

Nationwide Children's Hospital

[+1]

100 Clinical Results associated with BMI1

100 Translational Medicine associated with BMI1

0 Patents (Medical) associated with BMI1

2,506

Literatures (Medical) associated with BMI1

01 Dec 2025·Molecular Biology Reports

Are rs1042059 and rs11591377 polymorphisms of BMI1 gene related to leukemia?

Article

Author: Tahannejad Asadi, Zari ; Kaydani, Gholam Abbas ; Eftekhar, Zeinab ; Abbasi Farid, Amir Bahador ; Jalali Far, Mohammad Ali ; Amirrajab, Nasrin

INTRODUCTIONHematologic malignancies, originating from uncontrolled growth of hematopoietic and lymphoid tissues, constitute 6.5% of all cancers worldwide. Various risk factors including genetic disorders and single nucleotide polymorphisms play a role in the pathogenesis of hematologic malignancies. BMI1 is one of the genes involved in regulating the self-renewal and differentiation of hematopoietic stem cells.MATERIALS AND METHODS69 leukemia patients (45 AML, 18 ALL, and 6 CML) along with 80 control samples were selected. The frequency of rs1042059 and rs11591377 polymorphisms of BMI1 gene was evaluated using the Tetra-ARMS PCR technique.RESULTSA significant difference in the prevalence of rs1042059 and rs11591377 polymorphisms was observed between the patient and control groups (P = < 0.001). The frequency of GA genotypes for both polymorphisms was higher in patients compared to the control group. Additionally, a significant difference was found in the prevalence of rs11591377 genotypes among the AML, ALL, and CML groups (P = 0.002) however, no significant difference was observed in the prevalence of rs1042059 genotypes among them (P = 0.578).CONCLUSIONSConsidering the significant decrease in the prevalence of allelic variants in the control group compared to the leukemia group, the association of BMI1 with leukemias should be considered as a diagnostic and prognostic factor.

01 Dec 2025·Histochemistry and Cell Biology

Polycomb protein Bmi1 promotes odontoblast differentiation by accelerating Wnt and BMP signaling pathways

Article

Author: Ninomiya, Tadashi ; Kitamura, Chiaki ; Hosoya, Akihiro ; Seki-Kishimoto, Yuri ; Yukita, Akira ; Nakamura, Hiroaki ; Takebe, Hiroaki ; Iijima, Masahiro ; Noguchi, Yukiko ; Yoshiba, Nagako ; Washio, Ayako ; Morotomi, Takahiko

Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4 days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1 week, whereas their immunoreactivity was not detected after 8 weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways.

01 Jun 2025·Experimental Eye Research

Limbal explant cultures on amniotic membrane: The effects of passaging the explants on cell phenotype

Article

Author: Gurdal, Mehmet ; Selver, Ozlem Barut ; Durak, Ismet ; Baysal, Kemal

In vitro expansion of limbal epithelial stem cells (LESCs) while maintaining their characteristics has the potential to address the urgent need in ophthalmology clinics for the treatment of limbal stem cell deficiency (LSCD). Herein, we investigated the impact of explant passaging on the phenotype of LESCs cultured on human amniotic membrane (hAM). Following initial coverage of the hAM surface by cells (passage 0), the rabbit limbal explants underwent two additional passages. Expanded cells were then counted using a hemocytometer and examined by immunocytochemistry and RT-qPCR to assess markers associated with LESCs (ABCG2, P63, CK14, CXCR4, BMI-1, and vimentin) and differentiated LESCs (CK3 and connexin 43). The cell yield of passage 1 was the highest among all passages. Immunocytochemistry analysis revealed that the number of CK14-positive cells was similar across all passages; vimentin-positive cells were the lowest in passage 0, while vimentin-positive cells were the highest in passage 1; and CK3-positive cells were the highest in passage 0. RT-qPCR analysis revealed that CK3 and connexin 43 expression was significantly higher in passage 0 cells than in passage 2 cells; and CXCR4 and BMI-1 expressions were significantly higher in passage 1 cells than in passage 0 cells. Our data highlight that the passaging of limbal explant on hAM results in varying cell characteristics. The decrease in CK3 and increase in ABCG2 expression in cells obtained by passaging the limbal explant suggest that passaging could potentially enhance the stem cell population within the in vitro limbal explant culture on hAM.

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