Amkl

Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease with extremely poor outcome. We performed single-cell RNA sequencing (scRNA-seq) of the bone marrow from two CBFA2T3-GLIS2 fusion-positive and one RBM15-MKL1 fusion-positive non-DS-AMKL children. Meanwhile, we downloaded the scRNA-seq data of normal megakaryocyte (MK) cells of the fetal liver and bone marrow from healthy donors as normal controls...

Objective: To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) . Methods: Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology...

Acute megakaryoblastic leukaemia (AMKL) is characterized by expansion of megakaryoblasts, which are hyper-proliferative cells that fail to undergo differentiation. Insight to the cell-cycle regulation revealed important events in early or late megakaryocytes (MKs) maturation; the cyclin-dependent kinases 4 and 6 (CDK4/6) have been reported to participate in the development of progenitor megakaryocytes, mainly by promoting cell cycle progression and DNA polyploidization. However, it remains unclear whether the continuous proliferation, but not differentiation, of megakaryoblasts is related to an aberrant regulation of CDK4/6 in AMKL...

Individuals with Down syndrome (DS) have more than 100-fold increased risk of acute megakaryoblastic leukemia (AMKL), but its pathogenesis is poorly understood. In this issue of the JCI, Arkoun et al. engineered stepwise DS-AMKL-associated mutations in GATA1, MPL, and SMC3 in human induced pluripotent stem cell (iPSC) clones from individuals with DS to dissect how each mutation affects gene expression control and megakaryocytic differentiation. The authors showed that the mutations cooperatively promote progression from transient myeloproliferative disorder to DS-AMKL...

Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL)...

Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations. We modelled the megakaryocyte differentiation defect through stepwise gene editing of GATA1s, SMC3+/- and MPLW515K providing 20 different trisomy or disomy 21 iPSC clones. GATA1s profoundly reshaped iPSC-derived hematopoietic architecture with gradual myeloid-to-megakaryocyte shift and megakaryocyte differentiation alteration upon addition of SMC3 and MPL mutations...

Thrombocytopenia is a frequent occurrence in a variety of hematopoietic diseases; however, the details of the mechanism leading to low platelet count remain elusive. Megakaryocytes are a series of progenitor cells responsible for the production of platelets. Alterations in megakaryocytes in the bone marrow are a causative factor resulting in thrombocytopenia in varied diseases. Based on ultrastructural analysis of incidentally encountered megakaryocytes in 43 patients with blood diseases marked by low platelet counts, electron micrographs demonstrated that aberrant megakaryocytes predominated in idiopathic thrombocytopenic purpura, aplastic anemia, and myelodysplastic syndrome; autophagy, apoptosis, and cellular damage in megakaryocytes were a prominent feature in aplastic anemia...

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL. AMKL patients were subdivided into transient abnormal myelopoiesis (TAM), myeloid leukemia associated with Down syndrome (ML-DS), AML-not otherwise specified with megakaryocytic differentiation (NOS-AMKL), and AMKL-other patients (AML patients with other WHO classification but with flowcytometric features of megakaryocytic differentiation)...

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Chimeric antigen receptor (CAR) T-cell therapy combines antigen-specific properties of monoclonal antibodies with the lytic capacity of T cells. An effective and safe CAR-T cell therapy strategy relies on identifying an antigen that has high expression and is tumor specific. This strategy has been successfully used to treat patients with CD19 + B-cell acute lymphoblastic leukemia (B-ALL). Finding a suitable target antigen for other cancers such as acute myeloid leukemia (AML) has proven challenging, as the majority of currently targeted AML antigens are also expressed on hematopoietic progenitor cells (HPCs) or mature myeloid cells...

INTRODUCTION: GATA1 mutation plays an important role in initiating transient abnormal myelopoiesis (TAM) and in the clonal evolution towards acute megakaryoblastic leukaemia (AMKL) associated with Down syndrome (DS). This study aimed to develop and validate the clinical utility of a complementary DNA (cDNA) analysis in parallel with the conventional genomic DNA (gDNA) Sanger sequencing (Ss), as an initial screening test for GATA1 mutations. METHODS: GATA1 mutations were evaluated using both gDNA and cDNA in 14 DS patients using Ss and fragment analysis (FA), respectively...

Given the plasticity of hematopoietic stem/progenitor cells, multiple routes of differentiation must be blocked during acute myeloid leukemia pathogenesis - the molecular basis of which is incompletely understood. Here we report that post-transcriptional repression of the transcription factor ARID3A by miR-125b is a key event in megakaryoblastic leukemia (AMKL) pathogenesis. AMKL is frequently associated with trisomy 21 and GATA1 mutations (GATA1s), and children with Down syndrome are at a high risk of developing this disease...

Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS)...

OBJECTIVE: To explore the phenotypic and genetic characteristics of acute megakaryoblastic leukemia (AMKL) in young children accompany by WT1, MLL-PTD and EVI1, in order to improve the diagnosis level of AMKL. METHODS: EDTA-K2 anticoagulation venous blood was collected for blood routine and morphological analysis of blood cells; bone marrow was extracted for cell morphology, immunophenotype, chromosome karyotype and fusion gene analysis. RESULTS: White blood cell count was 12...

Cohesin is a multisubunit protein complex that forms a ring-like structure around DNA. It is essential for sister chromatid cohesion, chromatin organization, transcriptional regulation, and DNA damage repair and plays a major role in dynamically shaping the genome architecture and maintaining DNA integrity. The core complex subunits STAG2, RAD21, SMC1, and SMC3, as well as its modulators PDS5A/B, WAPL, and NIPBL, have been found to be recurrently mutated in hematologic and solid malignancies. These mutations are found across the full spectrum of myeloid neoplasia, including pediatric Down syndrome-associated acute megakaryoblastic leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and de novo and secondary acute myeloid leukemias...

OBJECTIVE: To study the clinical features and prognosis of children with acute megakaryocytic leukemia (AMKL) and the clinical effect of acute myeloid leukemia 03 (AML03) regimen for the treatment of pediatric AMKL. METHODS: The clinical data were collected from 47 children with AMKL who were diagnosed from May 2011 to December 2019. The treatment outcomes and prognostic factors were analyzed. The Kaplan-Meier method and the log-rank test were used for survival analysis...

Acute megakaryocytic leukemia (AMKL) is one of the rarest sub-types of acute myeloid leukemia (AML). AMKL is characterized by high proliferation of megakaryoblasts and myelofibrosis of bone marrow, this disease is also associated with poor prognosis. Previous analyses have reported that the human megakaryoblastic cells can be differentiated into cells with megakaryocyte (MK)-like characteristics by phorbol 12-myristate 13-acetate (PMA). However, little is known about the mechanism responsible for regulating this differentiation process...

Long noncoding ribonucleic acids (lncRNAs) are ribonucleic acid (RNA) molecules longer than 200 nucleotides without protein-coding capacity. Several studies have shown that lncRNAs play a pivotal role in the initiation, maintenance, and progression of acute myeloid leukemia (AML), which could make them a promising candidate in the diagnosis and treatment of leukemia. Acute Megakaryoblastic leukemia (AMKL) is a rare form of AML with a poor prognosis and low survival. It has been reported that lncRNA MIR100HG is involved several types of malignancies...

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia but is approximately 500 times more likely to develop in children with Down syndrome (DS) through transformation of transient abnormal myelopoiesis (TAM). This study investigates the clinical significance of genomic heterogeneity of AMKL in children with and without DS and in children with TAM. Genomic evaluation of nine patients with DS-related TAM or AMKL, and six patients with non-DS AMKL, included conventional cytogenetics and a comprehensive next-generation sequencing panel for single-nucleotide variants/indels and copy-number variants in 118 genes and fusions involving 110 genes...

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia accompanied by an aggressive clinical course and dismal prognosis. We herein report a case of AMKL preceded by mediastinal germ cell tumor that relapsed early after allogeneic hematopoietic stem cell transplantation with myeloablative conditioning but was successfully treated using salvage cord blood transplantation (CBT) with reduced-intensity conditioning. Although several serious complications developed, sustained remission with a favorable general condition was ultimately achieved...