Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia.

Introduction: This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML.

Methods: Endpoints included complete remission rate (CRR), overall response rate (ORR), overall survival (OS) and safety.

Results: Eighteen and 36 patients were enrolled into the unfit and R/R AML arms, respectively.

Comprehensive Age-Stratified Impact of Mutation in Acute Myeloid Leukemia: A Real-World Experience.

While -mutated AML in the absence of -ITD generally carries a favorable prognosis, large registry studies suggest the positive prognostic benefit may not extend to patients > 65 years of age. We examined this preferential, age-dependent prognostic impact through a real-world analysis of 2811 adult AML patients. The median overall survival (OS) was significantly better in compared to patients [20.

Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions.

Germline mutations in the gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A ()-gene-rearranged and -m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed/refractory setting.

Paroxysmal nocturnal hemoglobinuria-related thrombosis in the era of novel therapies: a 2043-patient-year analysis.

Thrombophilia is one of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anticomplement treatment has revolutionized the natural history of PNH, with control of the hemolytic process and abolition of thrombotic events (TEs). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anticoagulation depending on individual practices.

Late Presentation of Dyskeratosis Congenita: Germline Predisposition to Adult-Onset Secondary Acute Myeloid Leukemia.

Classic dyskeratosis congenita is a hereditary disease where the majority of patients present with bone marrow failure and mucocutaneous changes: mainly skin pigmentation, nail dystrophy, oral premalignant leukoplakia, in addition to increased risk for malignancies. A 63-year-old man with a long history of untreated chronic pulmonary disease, a smoker in the past, presented initially with pancytopenia and a clinical diagnosis of myelodysplastic syndrome with excess blasts returned a month later with leukocytosis (WBC 215.9 × 10/μL) and diagnosed with acute myeloid leukemia (AML) with deletion of chromosome 7 and -TKD mutation.

Selective inhibition of nuclear export: a promising approach in the shifting treatment paradigms for hematological neoplasms.

Novel targeted therapeutics alone or in rational combinations are likely to dominate the future management of various hematological neoplasms. However, the challenges currently faced are the molecular heterogeneity in driver lesions and genetic plasticity leading to multiple resistance pathways. Thus, progress has overall been gradual.

PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin's lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence.

Circular RNAs in acute myeloid leukemia.

Although mechanistic studies clarifying the molecular underpinnings of AML have facilitated the development of several novel targeted therapeutics, most AML patients still relapse. Thus, overcoming the inherent and acquired resistance to current therapies remains an unsolved clinical problem. While current diagnostic modalities are primarily defined by gross morphology, cytogenetics, and to an extent, by deep targeted gene sequencing, there is an ongoing demand to identify newer diagnostic, therapeutic and prognostic biomarkers for AML.

Fanconi Anemia germline variants as susceptibility factors in aplastic anemia, MDS and AML.

Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), aplastic anemia (AA), and related conditions for the presence of germline (GL) alterations in Fanconi Anemia (FA) and telomerase genes. We have detected an increased frequency of heterozygous FA gene mutations in MDS and to lesser degree in AML suggesting that the presence of one normal allele may not be completely protective and indeed heterozygous FA lesions may have a long latency period before hematologic manifestation. In contrast, GL telomerase gene mutations were not associated with increased disease risk.

Rational management approach to pure red cell aplasia.

Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas.

Inflammatory Changes in Lung Tissues Associated with Altered Inflammation-Related MicroRNA Expression after Intravenous Administration of Gold Nanoparticles .

Potential adverse effects of gold nanoparticles (AuNPs) are gaining attention due to their wide industrial, consumer, and biomedical applications. This may give rise to possible health risks from direct exposure to the NPs. Excessive inflammatory response is known to be one of the main effects induced by NPs.