PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “MENIN”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

11 recordsLinked to original sources
PubMed2025

Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition.

Targeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, the rapid development of menin inhibitor resistance calls for combinatory strategies to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) of MLLr acute myeloid leukemia (AML) exhibit enhanced guanine nucleotide biosynthesis, the inhibition of which leads to myeloid differentiation and sensitization to menin inhibitors. Mechanistically, targeting inosine monophosphate dehydrogenase 2 (IMPDH2) reduces guanine nucleotides and rRNA transcription, leading to reduced protein expression of LEDGF and menin. Consequently, the formation and chromatin binding of the MLL-fusion complex is impaired, reducing the expression of MLL target genes. Inhibition of guanine nucleotide biosynthesis or rRNA transcription further suppresses MLLr AML when combined with a menin inhibitor. Our findings underscore the requirement of guanine nucleotide biosynthesis in maintaining the function of the LEDGF/menin/MLL-fusion complex and provide a rationale to target guanine nucleotide biosynthesis to sensitize MLLr leukemias to menin inhibitors.

Proto-Oncogene Proteins↗
PubMed2025

KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.

UNLABELLED: NUP98 fusion oncoproteins (FO) are a hallmark of childhood acute myeloid leukemia. NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. In this study, we show that MYST family histone acetyltransferase (HAT) complex proteins, including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1, associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of KAT6A and KAT7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with menin inhibitor treatment, and was efficacious in menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r acute myeloid leukemia. SIGNIFICANCE: KAT6A and KAT7 associate with NUP98 FOs to drive leukemogenesis. Inhibition of their HAT activity is an effective therapeutic strategy in NUP98-r leukemias, including those resistant to menin inhibition. Moreover, combined KAT6A/7 and menin inhibition is synergistic, supporting clinical translation to improve outcomes for NUP98 FO-driven leukemias.

Humans↗
PubMed2026

Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions.

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.

BCL2↗
PubMed2026

Acute leukemia therapy at a crossroads: from conventional chemotherapy to the era of precision medicine.

Since the discovery of cytotoxic agents in the mid-20th century, acute leukemia has consistently served as a model for oncology research. As the Human Genome Project and subsequent genomic profiling elucidated the landscape of somatic mutations and cytogenetic aberrations driving leukemogenesis, the development of molecularly targeted therapies has dramatically accelerated, yielding significant improvements in patient outcomes. In acute myeloid leukemia (AML), the emergence of selective inhibitors targeting high-frequency alterations such as FLT3, NPM1, and IDH1/2 has redefined the standard of care, demonstrating superior efficacy when combined with conventional intensive chemotherapy or hypomethylating agents. Simultaneously, for acute lymphoblastic leukemia (ALL), in addition to the significant improvements achieved by tyrosine kinase inhibitors (TKIs) for BCR-ABL-positive ALL, the advent of CD19- or CD22-targeted monoclonal antibodies and CAR-T cell therapies has marked an epoch-making milestone, representing a major paradigm shift in the management of relapsed or refractory cases. Bridging these two distinct lineages, menin inhibitors have emerged as a novel class of agents targeting a common pathogenic mechanism in KMT2A-rearranged AML/ALL and NPM1-mutated AML, exhibiting promising antileukemic activity across these subtypes. In this review, we describe the evolution of leukemia therapy-highlighting historical trajectory across AML, APL, and ALL from uniform cytotoxic chemotherapy to molecularly targeted agents, antibody-based therapies, and chemo-free paradigms, while outlining future perspectives for precision hematology.

Acute lymphoblastic leukemia↗
PubMed2026

Evolving Management Approaches Toward Personalized Therapy in Acute Myeloid Leukemia: A Narrative Review.

After many years of stagnation in the treatment of acute myeloid leukemia (AML), there is currently a rapid move towards personalized medicine. Improvements in molecular diagnostics, risk assessment tools, targeted therapies, overall patient fitness assessments, and quality-of-life assessments have significantly changed how patients are treated. Genetic and molecular analyses, risk and health assessments, and measurable residual disease (MRD) monitoring are now integral to the treatment plan for evaluating patient responses and recurrence. In this regard, lower-intensity treatments are provided to older or unfit individuals. On the other hand, younger patients are usually subjected to curative therapies such as intensive chemotherapy to induce remission. Depending on their fitness and disease risk, they can be considered for hematopoietic cell transplantation, which is done after close observation for MRD. In addition, newer therapeutic drugs and immunotherapy techniques are being applied for patient management. Tremendous strides have been made in improving the efficiency of treatment programs in the relatively new area of personalized AML therapy, with a focus on functionality.

CPX-351↗
PubMedDate not supplied

[Epidemiology of group A beta-hemolytic streptococcus in the school population of Pordenone Province].

During the winter months of 1976-1977, our group carried out an epidemiological study in the school population aged 7 years and 10 years respectively, living in the towns of Pasiano (pop. 6,389) and Zoppola (pop. 7,383) in the province of Pordenone. The aim of the study was to determine the incidence of individuals in the school-age group having group A beta haemolitic streptococcus in the pharynx. The results of the study showed a high incidence of children with a positive throat swad. Of the 284 scholars examined, 107 (45.7% of the entire population examined) were carriers, in the pharynx, of group A beta haemolytic streptococcus.

Carrier State↗
PubMed1979

Enterogastric reflux in normal subjects and patients with Bilroth II gastroenterostomy. Measurement of enterogastric reflux.

Initially, scintigraphy was established as a valid method for detecting and quantitating enterogastric reflux. A new, tubeless technique for the measurement of enterogastric reflux was developed. 99mTc bound to [(2,6 dimethylphenylcarbamoylmethyl) iminodiacetic acid] (5 mCi) was administered intravenously to visualize the liver and biliary tract. One hour later, a standard liquid meal labeled with 111In bound to diethylene-triamine penta-acetic acid (250 microCi) was given. The 99mTc and 111In activities were recorded simultaneously for 1-min periods at 15-min intervals for 2 hr over liver, gallbladder, and gastric areas of interest. Enterogastric reflux indices were determined. Ten normal subjects and 13 patients with vagotomy, hemigastrectomy, and Bilroth II gastrojejunostomy were evaluated. The enterogastric reflux index in asymptomatic postsurgical patients was increased significantly to 24.6 +/- 4.7 compared with 8.2 +/- 6.0 (P less than 0.01) in normal subjects. In postsurgical patients with the syndrome of alkaline gastritis, the enterogastric reflux index was increased significantly to 86.3 +/- 7.1 (P less than 0.01) compared with asymptomatic postsurgical patients.

Esophagitis, Peptic↗
PubMedDate not supplied

[Body weight, body height and menarche. Epidemiological study, in the Province of Pordenone, of the school population from 12 to 15 years old (12,000)].

The relation between body weight, height and the commencement of menstruation was studied in 5324 girls aged 12--15 yr attending secondary schools in the province of Pordenone. The mean age of menarche was 12 2/12 yr and varied little throughout the province. Weight and height appeared closely related to menarche. A threshold of 49.2 kg and 157.3 cm was noted. Attainment of these critical values was apparently the factor that influenced the age at which menstruation commenced.

Adolescent↗