Clinical outcomes of early WT1 mRNA reduction after remission induction in newly diagnosed acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation.

Background: Wilms' Tumor (WT1) mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of WT1 mRNA after initial remission induction of patients with AML who have received transplant treatments.

Objective: Thus, we retrospectively analyzed the clinical features and prognostic impact of WT1 mRNA reduction in patients with AML after initial remission induction at our hospital.

Unveiling the Link Between NADPH Oxidase 2 Activation and Mitochondrial Superoxide Formation in Leukemic Cell Killing Induced by Arsenic Trioxide.

This study focused on the interplay between NADPH oxidase 2 (NOX 2) activation and mitochondrial superoxide (mitoO) formation induced by clinically relevant concentrations of arsenic trioxide (ATO; AsO) in acute promyelocytic leukemia (APL) cells. Carefully controlled inhibitor studies and small interfering RNA mediated downregulation of p47 (a component of the NOX 2 complex) expression demonstrated that, in an APL cell line, ATO promotes upstream NOX 2 activation critically connected with the formation of mitoO and with the ensuing mitochondrial permeability transition (MPT)-dependent apoptosis. Instead, acute myeloid leukemia (AML) cell lines respond to ATO with low NOX 2 activation, resulting in a state that is non-permissive for mitoO formation.

Double mutant DNMT3A AML: a unique subtype experiencing increased DNA damage and poor prognosis.

Mutation of DNMT3A, encoding a de novo methyltransferase essential for cytosine methylation, is a common early event in clonal hematopoiesis (CH) and adult acute myeloid leukemia (AML). Spontaneous deamination of methylated cytosines damages DNA, which is repaired by the base excision repair (BER) enzymes MBD4 and TDG. Congenital MBD4-deficiency has been linked to early-onset CH and AML, and is marked by exceedingly high levels of DNA damage and mutation of DNMT3A.

Evaluating the effect of acute myeloblastic leukemia-derived exosomes on the human bone marrow mesenchymal stromal cell proliferation.

Background: The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM.

Methods And Results: hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line.

Acute myeloid leukemia and myelodysplastic neoplasms: clinical implications of myelodysplasia-related genes mutations and TP53 aberrations.

Purpose: The fifth World Health Organization (WHO) classification (2022 WHO) and International Consensus Classification (ICC) of myeloid neoplasms have recently been published. In this study, patients were reclassified according to the revised classification and their prognoses were analyzed to confirm the clinical utility of the new classifications.

Methods: We included 101 adult patients, 77 with acute myeloid leukemia (AML) and 24 with myelodysplastic neoplasms (MDS), who underwent bone marrow aspiration and next-generation sequencing (NGS) between August 2019 and July 2023.

Essential thrombocytosis transformed AML with TP53 mutations and its clinical implications.

Essential thrombocytosis (ET) is a chronic myeloproliferative neoplasm. There is a rare possibility of its transformation from ET into acute myeloid leukemia (AML). While the TP53 mutation is a well-known risk factor for AML, limited research exists regarding ET patients who develop AML with TP53 mutations.

Antisense oligonucleotides as a targeted therapeutic approach in model of acute myeloid leukemia.

Background: The genetic and epigenetic alterations observed in acute myeloid leukemia (AML) contribute to its heterogeneity, influencing disease progression response to therapy, and patient outcomes. The use of antisense oligonucleotides (ASOs) technology allows for the design of oligonucleotide inhibitors based on gene sequence information alone, enabling precise targeting of key molecular pathways or specific genes implicated in AML.

Methods And Results: Midostaurin, a FLT3 specific inhibitor and ASOs targeting particular genes, exons, or mutations was conducted using AML models.

Acute lower limb ischemia revealing hypo granular acute promyelocytic leukemia.

Introduction: Acute promyelocytic leukemia (AML-M3), classified as acute Myeloid leukemia with PML RARA according to the 5th edition of the World Health Organization classification of haematolymphoid tumors 2022 [1], is marked by abnormal promyelocyte proliferation and is known for high risks of bleeding and thromboembolic complications. We present a case where lower limb ischemia revealed this leukemia in a child.

Case Report: An 11-year-old with minor ankle trauma developed severe lower limb ischemia, leading to the discovery of subtotal femoral artery thrombosis.

rearranged acute myeloid leukemia transformed from V617F mutated primary myelofibrosis.

Acute myeloid leukemia (AML) with fusion is rare with largely unknown clinicopathological features and genomic characterization. We present one such case of AML transformed from V617F mutated primary myelofibrosis and review the literature on this topic. The immunophenotype and the landscape of cooperative gene alterations in AML with resemble those of AML with , including expression of CD19, cooperative gene alterations in signaling pathway (), epigenetic/chromatin and cell cycle regulation (, , and ), and additional chromosomal abnormalities (trisomies 8 and 15).

Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report.

Introduction: Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells.

A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice.

Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates.

Exosome-Shuttled METTL14 From AML-Derived Mesenchymal Stem Cells Promotes the Proliferation and Radioresistance in AML Cells by Stabilizing ROCK1 Expression via an m6A-IGF2BP3-Dependent Mechanism.

Acute myelogenous leukemia (AML)-derived mesenchymal stem cells (MSCs) (AML-MSCs) have been identified to play a significant role in AML progression. The functions of MSCs mainly depend on their paracrine action. Here, we investigated whether AML-MSCs functioned in AML cells by transferring METTL14 (Methyltransferase 14) into AML cells via exosomes.

Functions of the native NPM1 protein and its leukemic mutant.

The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30-35% of adult acute myeloid leukemia (AML).

CPX-351 plus gemtuzumab ozogamicin for relapsed/refractory acute myelogenous leukemia: a University of California Hematologic Malignancies Consortium trial.

In this multicenter phase Ib trial, we investigated the combination of CPX-351 and gemtuzumab ozogamicin (GO) in relapsed/refractory acute myeloid leukemia (AML). Cohort A received CPX-351 plus a single dose of GO, while cohort B received two doses of GO. Thirteen participants received investigational treatment.

Cellular heterogeneity and cytokine signatures in acute myeloid leukemia: A novel prognostic model.

Acute Myeloid Leukemia (AML) is a complex hematological malignancy distinguished by its heterogeneity in genetic aberrations, cellular composition, and clinical outcomes. This diversity complicates the development of effective, universally applicable therapeutic strategies and highlights the necessity for personalized approaches to treatment. In our study, we utilized high-resolution single-cell RNA sequencing from publicly available datasets to dissect the complex cellular landscape of AML.

IRX-related homeobox gene MKX is a novel oncogene in acute myeloid leukemia.

Homeobox genes encode transcription factors which organize differentiation processes in all tissue types including the hematopoietic compartment. Recently, we have reported physiological expression of TALE-class homeobox gene IRX1 in early myelopoiesis restricted to the megakaryocyte-erythroid-progenitor stage and in early B-cell development to the pro-B-cell stage. In contrast, sister homeobox genes IRX2, IRX3 and IRX5 are aberrantly activated in the corresponding malignancies acute myeloid leukemia (AML) and B-cell progenitor acute lymphoid leukemia.

mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia.

The DNA demethylating therapy with azacitidine (AZA) is a promising therapeutic strategy for elderly patients with acute myeloid leukemia (AML). AZA primarily inhibits DNA methylation, promotes cell differentiation and apoptosis in AML. However, as a cytosine nucleoside analog, AZA also has the potential to be incorporated into RNA molecules.

The high-risk model associated with SYTL4 predicts poor prognosis and correlates with immune infiltration in AML.

Acute myeloid leukemia (AML) currently lacks a definitive cure. Studies have highlighted the involvement of SYTL4 expression levels in neoplasms, yet its specific roles in AML remain unexplored in the literature. Utilizing the TCGA and XENA databases, this study investigated SYTL4 expression levels in AML and identified associations between SYTL4 overexpression and clinicopathological features, prognosis, and immune infiltration in AML patients through genomic analysis.

Incidence, characteristics and outcome of therapy-related myeloid neoplasms in women with epithelial ovarian cancer after exposure to poly-ADPribose polymerase inhibitors: A cancer center experience.

Poly(ADP-ribose) polymerase inhibitors (PARPi) target the DNA repair pathways and have been established in epithelial ovarian cancer (EOC) as maintenance therapy inducing prolonged survival. However, recently published data showed that PARPi may increase the risk of therapy-related myeloid neoplasms (t-MN) including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Herein, we investigated the incidence, characteristics, and management of t-MN among EOC patients after exposure to PARPi in a Greek Cancer Center.

Nurse-Led Interventions for Improving Medication Adherence in Chronic Diseases: A Systematic Review.

: Poor medication adherence results in negative health outcomes and increased healthcare costs. Several healthcare professionals provide interventions to improve medication adherence, with the effectiveness of nurse-led interventions in people with chronic diseases remaining unclear. : This study sought to evaluate the effectiveness of nurse-led interventions for improving medication adherence in adults with chronic conditions.

Calaspargase-Pegol-Mknl Combined with BCL-2 and MCL-1 Inhibition for Acute Myeloid Leukemia.

Our previous studies have demonstrated that pegcrisantaspase (PegC), a long-acting asparaginase, synergizes with the BCL-2 inhibitor Venetoclax (Ven) in vitro and in vivo; however, the anti-leukemic activity of -derived asparaginases in combination with BCL-2 inhibition, and potential synergy with inhibitors of MCL-1, a key resistance factor of BCL-2 inhibition, has yet to be determined. Using a combination of human AML cells lines, primary samples, and in vivo xenograft mouse models, we established the anti-leukemic activity of the BCL-2 inhibitor S55746 and the MCL-1 inhibitor S63845, alone and in combination with the long-acting asparaginase calaspargase pegol-mknl (CalPegA). We report that CalPegA enhances the anti-leukemic effect of S55746 but does not impact the activity of S63845.

Characterization of the Bone Marrow Lymphoid Microenvironment and Discovery of Prognostic Immune-Related Factors in Acute Myeloid Leukemia.

Given the limited comprehensive data on the bone marrow (BM) immune environment in acute myeloid leukemia (AML), we analyzed the distribution and phenotype of T cell subsets, including γδ T cells, and their immune checkpoint (IC) ligands on blasts. We performed multiparametric flow cytometry with BM samples taken from 89 AML patients at the time of diagnosis, remission, and relapse/refractory status after chemotherapy and 13 healthy controls (HCs) to identify immune-related risk factors. Compared to the HCs, the T cells of the AML patients exhibited exhausted features including higher TIGIT levels and similar levels of PD-1 and TIM-3.

Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression?

Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of immune cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T cell senescence constitutes the primary mechanism underlying T cell dysfunction in acute myeloid leukemia (AML) and represents one of the potential causes of immunotherapy failure. AML usually progresses rapidly and is highly susceptible to drug resistance, thereby resulting in recurrence and patient mortality.