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Acute myeloid leukemia (AML) is an aggressive cancer affecting the blood and bone marrow that progresses rapidly, making immediate treatment essential. While chemotherapy and targeted drugs have improved outcomes for some patients, many forms of AML remain resistant to treatment, and relapses are common.

A new study sheds light on why certain types of AML are so challenging to treat and how outcomes for patients might be improved. Researchers from Japan, including scientists from Chiba University, have discovered that an epigenetic enzyme called SETD1B plays a critical role in supporting the growth of a particularly aggressive form of AML—especially in patients with the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutation, a genetic change associated with poor prognosis and high relapse rates. By targeting SETD1B, the researchers believe, it may be possible to develop more effective treatments that prevent leukemia cells from multiplying.

The study was led by Associate Professor Takayuki Hoshii and included Dr. Shintaro Izumi and Professor Atsushi Kaneda from the Graduate School of Medicine, Chiba University, Japan. The findings were published online in the journal Leukemia on May 8, 2025.

“Patients with AML, especially with the FLT3-ITD mutation, often respond poorly to current therapies. Our findings are that the epigenetic regulator SETD1B protein supports aggressive cell proliferation in AML by promoting oncogenic MYC expression,” says Dr. Hoshii.

Previous research has shown that FLT3-ITD mutations are detected in patients with mixed-lineage leukemia-rearranged (MLL-r) AML, a subtype of leukemia characterized by genetic abnormalities. MLL-r AML cells exhibit high levels of histone H3 lysine 4 trimethylation (H3K4me3), an epigenetic modification that affects which genes are turned on or off without changing the DNA sequence. Though the link between MLL-r AML and H3K4me3 has been established, the association between FLT3-ITD and H3K4me3 remains unclear.

Using advanced genetic screening tools, the team identified Setd1b as the gene responsible for producing a protein that adds methyl groups to histone H3 at lysine 4, resulting in the H3K4me3 epigenetic modification, and upregulation of Myc genes, which plays a critical role in regulating cell growth, division, and metabolism and can contribute to cancer development if altered.

To understand the role of SETD1B, the researchers performed CRISPR screening and then genetically engineered leukemia cells with altered versions of SETD1B, specifically deleting its catalytic domain, which is the active part of the protein responsible for the epigenetic modification of the DNA. They then used RNA sequencing and chromatin mapping to identify which genes and pathways were most affected.

Their experiments revealed that removing SETD1B’s catalytic domain significantly slowed cancer growth, particularly in leukemia cells with FLT3-ITD or NrasG12D mutations. It also caused a drop in the activity of genes in the MYC pathway. This suggests that without the epigenetic function of SETD1B, MYC cannot remain fully active, weakening the ability of the cancer cells to grow and divide.

“The breadth of H3K4me3 is crucial for transcriptional consistency, and MYC expression appears highly dependent on both the quality and quantity of transcriptional elongation,” says Dr. Hoshii. “Understanding SETD1B’s role in maintaining this epigenetic mark is critical for developing biomarkers and therapies for leukemia subtypes and other MYC-driven cancers.”

Interestingly, when the researchers reintroduced the Myc gene back into leukemia cells lacking SETD1B, the cancer cells began to grow again, but only partially, suggesting that SETD1B plays a broader role in MYC’s cancer-promoting activity.

This discovery paves the way for new treatment strategies. By targeting SETD1B or its epigenetic functions, scientists may be able to develop therapies that are especially effective for patients with FLT3-ITD mutations. As a possible next step, the researchers point to Chaetocin, an existing compound known to inhibit enzymes related to SETD1B. This could serve as a foundation for developing more selective SETD1B-targeted drugs. Measuring SETD1B activity in patients might also help doctors predict who would benefit most from these therapies.

As the search for better treatments continues, this study reveals how targeting the cancer’s epigenetic machinery could provide a new strategy to treat the disease, giving hope to patients with aggressive forms of AML.

Reference:

Izumi, S., Ohtani, K., Matsumoto, M. et al. Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia. Leukemia 39, 1627–1639 (2025). https://doi.org/10.1038/s41375-025-02638-y.

A group led by the Department of Neurosurgery at the Brain Research Institute, Niigata University, has successfully treated a patient with a brainstem glioma harboring a rare IDH2 mutation. The patient initially presented with a gradual loss of hearing in the left ear, and MRI showed a lesion at the left side of the brainstem, near the root exit zone of the left acoustic nerve. Initially, a brainstem glioma with H3K27M mutation was suspected. However, the gradual clinical course and unusual location of the brainstem glioma were considered atypical.

The patient underwent magnetic resonance spectroscopy in which 2-hydroglutarate, a marker for IDH mutation, was evident. Subsequently, the patient underwent a surgical biopsy, and pathological analysis revealed a rare IDH2 mutation. Although most brainstem gliomas with H3K27M mutation have an unmethylated MGMT promoter and thus are resistant to temozolomide, about 70% of IDH-mutant astrocytomas are known to have a methylated MGMT promoter and are sensitive to temozolomide.

A team led by Dr. Manabu Natsumeda successfully treated the patient with temozolomide and radiation, and the tumor dramatically shrank, and surprisingly, the patient’s hearing improved. The patient has been off treatment after 1 year of maintenance temozolomide treatment, but the tumor has not relapsed. “We were fortunate to detect IDH mutation in this patient, or else we would not have used temozolomide. This case illustrates the importance of screening by MRS for IDH mutation and a safe biopsy to determine the optimal treatment.” explains Dr. Natsumeda. The case report was published online in the journal Frontiers in Oncology on July 8, 2025.

Reference:

Takuya Okada, Case Report: Improved hearing in a rare, adult IDH2-mutant brainstem astrocytoma successfully treated with radiation and temozolomide, Frontiers in Oncology, https://doi.org/10.3389/fonc.2025.1555986

France: A new study has found that using a combination of multiplex PCR (mPCR) testing and serum procalcitonin levels to guide antibiotic management in critically ill patients with community-acquired pneumonia (CAP) did not significantly reduce antibiotic exposure or improve outcomes when compared to standard care. The findings of the MULTI-CAP randomized controlled trial were published on July 15, 2025, in Intensive Care Medicine by Dr. Guillaume Voiriot of Sorbonne Université, Assistance Publique – Hôpitaux de Paris, and his research team.

Researchers have identified in a new study published in JAMA that repeated low-dose treatment with lysergic acid diethylamide (LSD) is safe but not substantially symptom-reducing in adults with attention-deficit/hyperactivity disorder (ADHD). A randomized controlled trial evaluated the safety and efficacy of microdosing LSD among patients with moderate to severe ADHD, with no difference in improvement in symptoms between LSD and placebo. The study was conducted by Lorenz M. and fellow researchers.

Tripura- The Director of Medical Education (DME) Tripura is soon going to commence Round 1 of Tripura State National Eligibility and Entrance Test-Undergraduate (NEET UG) 2025 Counselling for admission to MBBS, BDS, BHMS & BAMS Courses in various colleges against the Tripura State Quota/Domicile seats.