Myeloid Leukemia - Science topic

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse i...

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, RUNX1‐FPD), caused by monoallelic deleterious germline RUNX1 variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM‐associated...

There is a limited information available on the clinical characteristics, treatment patterns and outcomes on older patients diagnosed with Acute Myeloid Leukemia (AML) in Latin-America. This multicenter retrospective study analyzed 269 patients over 60 years of age diagnosed with AML in Colombia, using data from RENEHOC-PETHEMA registry, from 2009...

Acute promyelocytic leukemia (APML) is one of the most curable leukemia subtypes, where the majority of patients achieve complete remission and also deep molecular remission after therapy, characterized by a PCR-undetectable state. Similarly, chronic myelogenous leukemia (CML) is a leukemia where, thanks to effective targeted treatment with tyrosin...

Background: Acute myeloid leukemia (AML) is an aggressive cancer with variable treatment responses. While clinical factors such as age and genetic mutations contribute to prognosis, recent studies suggest that CT attenuation scores may also predict treatment outcomes. This study aims to develop a nomogram combining clinical and CT-based factors to...

Background/Objectives: Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure–activity relationship (QSAR) model to predict the inhibitory potency (pIC50 value...

Thrombosis is one of the most frequent complications of cancer, with a potential impact on morbidity and mortality, particularly those with acute myeloid leukemia (AML). Therefore, effective thrombosis prevention is a crucial aspect of cancer management. However, preventive measures against thrombosis may carry inherent risks and complications. Con...

To investigate the role of ALKBH3 in acute myeloid leukemia (AML), we constructed an animal model of xenotransplantation of AML. Our study demonstrated that ALKBH3-mediated m1A demethylation inhibits ferroptosis in KG-1 cells by increasing ATF4 expression, thus promoting the development of AML. These findings suggest that reducing ALKBH3 expression...

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly underst...

Timeline and genetic analysis of a 55‐year‐old female with a family history of gastric cancer and multiple myeloma, who was diagnosed with AML and a germline CEBPA variant. image

As median age of patients with acute myeloid leukemia is 72 years, older patients continue to be a vulnerable cohort representing significant challenges in clinical practice. Patient-specific comorbidities as well as leukemia-specific unfavorable molecular- and cytogenetics confer even poorer outcomes. Treatment of AML therefore needs to be less to...

Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults ( ≤ 60 years) p...

The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3AINS) in AML, we here investigate the common characteristics of DNMT3A...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for treating high-risk acute leukemias in developing countries but is costly and complex. Our cost-effective protocol achieves promising results, with 12-month disease-free survival rates of 52% for acute lymphoblastic leukemia and 65% for acute myeloid leukemia, close to tho...

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX mode...

Acute Myeloid Leukemia (AML) with KMT2A rearrangements (KMT2Ar), found on chromosome 11q23, is often called KMT2A-rearranged AML (KMT2Ar-AML). This variant is highly aggressive, characterized by rapid disease progression and poor outcomes. Growing knowledge of epigenetic changes, especially lactylation, has opened new avenues for investigation and...

The prognosis of pediatric acute myeloid leukemia (AML) remains poor compared with pediatric acute lymphoblastic leukemia (ALL); accurate diagnosis and treatment strategies based on the genomic background are strongly needed. Recent advances in sequencing technologies have identified novel pediatric AML subtypes, including BCL11B structural variant...

Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.6 years) with R/R AML was to establish a prognostic risk score. Overall r...

Background: Acute myeloid leukemia (AML) is a common and aggressive form of leukemia, yet current treatment strategies remain insufficient. Venetoclax, a BH3-mimetic approved for AML treatment, induces Bcl-2-dependent apoptosis, though its therapeutic efficacy is still limited. Therefore, new strategies to enhance the effect of venetoclax are highl...

Acute myeloid leukemia (AML) is a genetically heterogeneous disease with high rates of relapse after initial treatment. Identifying measurable residual disease (MRD) following initial therapy is essential to assess response, predict patient outcomes, and identify those in need of additional intervention. Currently, MRD analysis relies on invasive,...

Background and aim Acute myeloid leukemia (AML) is a remarkably complex malignancy; with considerable genetic, epigenetic, and phenotypic heterogenicity. Circ-RNAs are a novel class of non-coding RNA. They may influence leukemia development and offer exciting possibilities for targeted AML diagnosis and therapy. This study aimed to detect circ_0002...

Introduction Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research. Met...

Myeloid sarcoma (MS) is an extramedullary localization of immature granulocyte cells that can occur in association with acute myeloid leukemia (AML). Gastrointestinal involvement is relatively common in MS, but exclusive colonic localization is a rare occurrence. Here, we report on a 53-year-old male patient affected by AML developing a severe abdo...

Introduction KMT2A -rearrangements define a subclass of acute leukemias characterized by a distinct gene expression signature linked to the dysfunctional oncogenic fusion proteins arising from various chromosomal translocations involving the KMT2A (also known as MLL1 ) gene. Research on the disease pathomechanism in KMT2A -rearranged acute leukemia...

Background Patients with lysine methyltransferase 2a (KMT2A)‐rearranged (KMT2A‐r) acute myeloid leukemia (AML) are assigned to intermediate‐risk and adverse‐risk categories at diagnosis. However, the value of molecular measurable residual disease (MRD) status in patients who have KMT2A‐r AML before allogeneic hematopoietic stem cell transplantation...

FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is rem...

Background Medical resources, especially blood products, were in short supply during the COVID-19. Less intensive therapy with hypomethylating agents/venetoclax (VEN) seems an effective treatment option for patients with acute myeloid leukemia (AML). Objectives To retrospectively analyze the efficacy and safety of VEN combined with azacitidine (AZ...

Acute myeloid leukemia (AML) as the second most common hematological malignancy remains currently incurable. In this study, we found the protein disulphide isomerase family (PDIs) was expressed in primary leukemia cells, with particular emphasis on ERP5 and ERP57. The compound PACMA31 demonstrated the ability to inhibit proliferation, enhance diffe...

Introduction: FLT3 inhibitors have demonstrated increased efficacy in patients with FLT3-mutated acute myeloid leukemia (AML). However, their effects on patients unfit for intensive chemotherapy remain undefined. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FLT3 inhibitors in AML patients unfit for intensive...

The aim of this study was to investigate the clinical features and outcomes of elderly patients with acute myeloid leukemia (AML) from a real word research. The clinical data of 223 consecutive elderly patients (aged ≥ 60 years) who were newly diagnosed with AML at our medical center between July 2017 and June 2022, including their clinical charact...

Recent experimental findings indicate that cancer stem cells originate from transformed very small embryonic-like stem cells. This finding represents an essential advancement in uncovering the processes that drive the onset and progression of cancer. In continuously growing cell lines, for the first time, our team’s follow-up research on leukemia,...

Background Patients with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA‐sAML) face a dismal prognosis. Methods The authors analyze the characteristics, therapeutic approaches, and outcomes of patients with HMA‐sAML from the Programa Español para el Tratamiento de Hemopatías Malignas...

Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of acute myeloid leukemia (AML). Direct depletion of MECOM using an endogenous auxin-inducible degron immediately upregulates expression of myeloid differentiation factor CEBPA. MECOM depletion is also accompanied by a severe loss of...

Aleukemic leukemia cutis (ALC) is a rather uncommon condition that is characterized by leukemic cell invasion into the skin which primarily precedes the peripheral blood and marrow infiltration by leukemic cells. We present a 35-year-old male with maculopapular skin lesions with a normal bone marrow and peripheral smear. Skin lesions were positive...

Background. RUNX1A is the shortest and least expressed of the RUNX1 three main isoforms (A, B, C); despite this, the leukemogenic role of its overexpression has been clearly described. Several studies have shown RUNX1A involvement in different blood cancers and pilot observations in acute leukemia have been reported. Methods. In this context, we ev...

Various prognostic models have been proposed to improve the accuracy of prognostic assessment for Myelodysplastic syndromes (MDS). Recently, the Molecular International Prognostic Scoring System (IPSS-M) has been developed. Here, we validated the accuracy of IPSS-M in Chinese MDS patients, and proposed a prognostic model more suitable for Chinese p...

Molecular assessment of measurable residual disease (MRD) in NPM1‐mutated AML patients is a powerful prognostic tool to identify the risk of relapse. There is limited data regarding MRD‐guided decisions against alloSCT in elderly patients and FLT3–ITD co‐mutation. We describe the outcome of NPM1‐mutated AML patients in whom alloSCT was deferred bas...

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM result...

Acute spinal subdural hematoma (ASSDH) is a rare complication following intrathecal chemotherapy; however, it has the potential to cause significant morbidity. We present the case of a child treated with intrathecal chemotherapy for acute myeloid leukemia. The child presented with pain and acute paralysis in the lower limbs a few hours after lumbar...

Background Relapsed acute myeloid leukemia (AML) and high‐risk myelodysplastic syndrome (HR‐MDS) are associated with a poor prognosis. It is unknown which re‐induction therapy provides the highest chance of durable remission. Commonly used therapies are high dose cytarabine (HiDAC) and triple therapy consisting of fludarabine, cytarabine, and idaru...

Venetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in...

Antibody-Drug Conjugates (ADCs) have emerged as a promising targeted therapy for cancer, combining the specificity of monoclonal antibodies with the potent cytotoxic effects of chemotherapy agents. This paper provides a comprehensive review of the fundamental mechanisms, clinical applications, and potential future developments of ADCs in the treatm...

Acute myeloid leukemia (AML) is the most prevalent subtype of acute leukemia in adults, posing crucial challenges in terms of prognosis, treatment, and relapse. This is particularly evident in elderly patients, who frequently present with comorbidities that complicate their clinical management. This paper examines small molecule therapies that have...

The discovery of gene BAALC, which is selectively expressed by hematopoietic stem cells, allows to study of pathogenesis and efficacy treatment of human AML and MDS in clinical settings at the level of Stem Cells. To simplify the situation, these cells were collected under a common category “BAALCdexpressing Leukemia Stem Cells” to evaluate their b...

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndr...

Introdução: as neoplasias hematológicas (NH) são um conjunto de doenças malignas que afetam células hematopoiéticas imaturas e maduras. Em estudos hematológicos publicados, as NH são normalmente divididas em leucemias, linfoma de hodgkin e não hodgkin e mieloma múltiplo, sendo assim, em análises epidemiológicas são comumente separadas de acordo com...

Background: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have NPM1 mutations. There is controversy regarding their prognosis and best therapy. Methods: We studied 150 subjects with these features using targeted regional sequencing. Prognostic stratification was carried out based on risk factors, and we assessed...

Outcomes of myeloproliferative neoplasms (MPN)‐associated acute leukaemias are dismal with conventional therapy. Approximately 20% of MPN‐associated acute leukaemias have mutations in isocitrate dehydrogenase (IDH). Olutasidenib, and inhibitor of IDH1, demonstrates important clinical benefits in MPN‐associated leukaemia with IDH1 mutation. Commenta...

Background Natural killer (NK) cell immunotherapy has shown promising therapeutic potential for acute myeloid leukemia (AML), especially with advancements in chimeric antigen receptor-engineered NK cells (CAR-NK) and artificial intelligence (AI). Despite these developments, the field lacks comprehensive bibliometric analyses to identify research ho...

Background The proportion of residual leukemic blasts after chemotherapy assessed by multiparameter flow cytometry, is an important prognostic factor for the risk of relapse and overall survival in acute myeloid leukemia (AML). This measurable residual disease (MRD) is used in clinical trials to stratify patients for more or less intensive consolid...

Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which con...

Background: The management of pediatric acute myeloid leukemia (AML) is based on the prognostic risk classification of initial leukemia. Targeted next-generation sequencing (NGS) is a reliable method used to identify recurrently mutated genes of pediatric AML and associated prognosis. Methods: In this study, we retrospectively evaluated the prog...

The management of patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) remains a challenge with few reliably effective treatments. Preclinical studies have shown that the inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling; both of which are relevant...

Purpose This study aimed to determine the frequency of regulatory T cells (Tregs) (CD4 ⁺ /FOXP3 ⁺ ) and indoleamine 2,3-dioxygenase (IDO) expression in patients with acute myeloid leukemia (AML). Methods This cross-sectional case–control study was conducted between Jan 2022 and Dec 2023. Bone marrow samples were collected from 20 healthy individua...