Myelodysplastic Syndrome

The present study delineates the genomic distribution of Kaiso in cancer cells, confirming its role as a factor with a complex mode of DNA binding and a strong association with CpG islands, particularly with methylated and eroded CpG islands, revealing a new potential Kaiso target gene-SQSTM1, involved in differentiation of acute myeloid leukemia cells. Furthermore, we discovered the existence of a new class of CpG islands characterized by wave-like DNA methylation.

P1/2, N=240, Recruiting, Aptose Biosciences Inc. | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Nov 2026

P3, N=640, Active, not recruiting, DKMS gemeinnützige GmbH | Recruiting --> Active, not recruiting | Trial completion date: Aug 2026 --> Dec 2026

FMNL1 plays a potential role in granulocyte differentiation and function, and its differential expression is linked to critical signaling pathways in leukemogenesis and inflammation. These findings highlight FMNL1's potential therapeutic implications in myeloid neoplasia, warranting further investigation.

P1/2, N=122, Completed, BerGenBio ASA | Active, not recruiting --> Completed

The revised classifications allow for a more detailed categorization based on genetic abnormalities, which may be helpful in predicting prognosis. AML with TP53 mutations is a new ICC category that has shown a high prognostic significance in a small number of cases.

P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=50, Active, not recruiting, Institut Paoli-Calmettes | Recruiting --> Active, not recruiting

P3, N=777, Active, not recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Trial primary completion date: Dec 2024 --> Oct 2025

P2, N=164, Active, not recruiting, Takeda | Trial completion date: Dec 2024 --> Mar 2025

Improved survival was observed with transplantation in groups DP2, DP7, and DP9. These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.

Knockdown of Laptm4b partially rescued Evi1-induced abnormal hematopoiesis in vivo. Thus, our study establishes a mouse model to investigate EVI1hi myeloid malignancies, demonstrating the significance of the EVI1-mediated KDM6B/H3K27me3/LAPTM4B signaling axis in their maintenance.

The patient underwent four cycles of azacitidine (AZA) therapy, followed by successful bone marrow transplantation (BMT)...The patient was discharged 47 days postoperatively. This case demonstrated the rapid progression of infective endocarditis following BMT, highlighting the need for prompt recognition and management.

The ICC diagnostic criteria are clinically significant for determining AML prognosis. In line with the changing treatment paradigm for AML, future research is needed to continuously validate diagnostic and risk stratification systems.

P2, N=39, Completed, University Hospital, Grenoble | Recruiting --> Completed | Trial completion date: Dec 2024 --> Oct 2024 | Trial primary completion date: Dec 2024 --> Oct 2024

P1/2, N=179, Active, not recruiting, AbbVie | Trial completion date: Dec 2025 --> Dec 2026

P2, N=27, Recruiting, University of Illinois at Chicago | Trial completion date: Nov 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2026

P=N/A, N=5000, Recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P=N/A, N=163, Recruiting, Peking University People's Hospital | Not yet recruiting --> Recruiting | Trial completion date: Aug 2027 --> Dec 2027 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Aug 2027 --> Dec 2027

P3, N=727, Completed, ECOG-ACRIN Cancer Research Group | Active, not recruiting --> Completed

He was initially diagnosed as donor-derived myelodysplastic syndrome (MDS) and treated with azacitidine, followed by secondary transplantation using unrelated BM, providing durable complete remission...DC-TAM is a rare UCBT-related complication which resembles MDS, but the identification of GATA1 mutation may be useful for its diagnosis. Our genetic analyses revealed that a pre-existing clone in UCB may contribute to the development of donor cell-derived hematologic neoplasms, highlighting the potential relevance of genetic screening of donor UCB.

We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation + allelic deletion or a single mutation with variant allele frequency (VAF) ≥40%; TP53 low risk (TP53LR) included a single TP53 mutation VAF.

P1/2, N=150, Recruiting, Disc Medicine, Inc | N=56 --> 150 | Trial completion date: Oct 2024 --> Sep 2026 | Trial primary completion date: Oct 2024 --> Sep 2026

P1/2, N=72, Recruiting, Chengdu FenDi Pharmaceutical Co., Ltd.

P1/2, N=6, Active, not recruiting, Thomas Jefferson University | Recruiting --> Active, not recruiting | N=37 --> 6

P1, N=29, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Dec 2024 | Trial primary completion date: Mar 2026 --> Dec 2024

P=N/A, N=140, Recruiting, University Hospital, Toulouse | Trial primary completion date: Sep 2024 --> Jun 2025 | Trial completion date: Sep 2024 --> Dec 2025

Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.

P3, N=48, Recruiting, Institut de Recherches Internationales Servier | Not yet recruiting --> Recruiting

Morphological abnormalities include MDS with low blasts, MDS with increased blasts and hypoplastic MDS. This revision provides a foundation for precise diagnosis and treatment of MDS, further restricting the application of immunosuppressive therapy and advancing genetic research in diagnostics and therapeutics.

Zilurgisertib exhibited a favorable pharmacokinetic profile amenable to once-daily dosing that can be administered without regard to food. Study results support further clinical development of zilurgisertib in patients.

Additionally, an IFN-responsive T cell population was linked to fueling inflammation in the stroma. Overall, these findings open new avenues for early intervention in hematological malignancies.

We describe the clinical course and the outcome with the use of avapritinib, midostaurin, and decitabine-cedazuridine. Trial Registration: ClinicalTrials.gov identifier: NCT00782067.

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Sep 2024 --> Jun 2025

P1, N=114, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=105, Recruiting, University of Virginia | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

Notch and PI-PLC signaling facilitate intercellular communication, TGF-β promotes quiescence and suppresses hematopoiesis, and NF-κB-driven inflammatory responses foster an environment detrimental to normal hematopoiesis. This review highlights the role of these pathways within the MDS microenvironment, driving the development and progression of the disease and paving the way for new possible therapeutic strategies.

The patient was started on nilotinib therapy...This case pinpoints the importance of comprehensive study when MDS is present with deletion 20q and a t(9;22), as it can be misdiagnosed as CML. While definitive therapeutic guidelines have yet to be established for this rare presentation of MDS, the use of tyrosine kinase inhibitors is under investigation.

Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.

There is evidence that these hot-spot mutations may have dominant negative or gain-of-function properties. Here we review this evidence and discuss its potential impact on patient outcomes and clinical management.

Luspatercept, which can reduce SMAD2/SMAD3-dependent signaling implicated in suppression of erythropoiesis, may obviate the need for red blood cell transfusion in MDS-RS for more than a year, thereby diminishing further iron loading. However, luspatercept cannot be expected to substantially reduce the existing iron overload.

Many newer therapies are on the horizon, including chimeric antigen receptor T/NK-cell therapies, mutated p53 reactivators, Fc fusion protein, and monoclonal antibodies targeting various myeloid antigens. This review summarizes the current approaches for myeloid disease with TP53 mutation and provides an overview of emerging nontransplant approaches.