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Alex Pezzotta, Mara Mazzola, Marco Spreafico, Anna Marozzi, Anna Pistocchi
The genes of the cohesin complex exert different functions, ranging from the adhesion of sister chromatids during the cell cycle, DNA repair, gene expression and chromatin architecture remodeling. In recent years, the improvement of DNA sequencing technologies allows the identification of cohesin mutations in different tumors such as acute myeloid leukemia (AML), acute megakaryoblastic leukemia (AMKL), and myelodysplastic syndromes (MDS). However, the role of cohesin dysfunction in cancer insurgence remains elusive...
2019: Frontiers in Cell and Developmental Biology
Kosuke Tamefusa, Koshiro Fukutake, Hisashi Ishida, Akihiro Tamura, Mikiya Endo, Kazuko Hamamoto, Yuhki Koga, Mutsuko Yamada, Kiichiro Kanamitsu, Kaori Fujiwara, Kana Washio, Akira Shimada
Acute megakaryoblastic leukemia in children without Down syndrome (non-DS AMKL) is considered to be a poor prognostic subtype in acute myeloid leukemia. Recently, some chimeric fusion genes were found in pediatric non-DS AMKL; therefore, we attempted to detect chimeric fusion genes RBM15-MKL1, CBFA2T3-GLIS2, and NUP98-KDM5A from 10 pediatric non-DS AMKL diagnostic samples using polymerase chain reaction and Sanger sequencing methods. Two samples were positive for RBM15-MKL1, four had CBFA2T3-GLIS2, and only one case had NUP98-KDM5A...
2019: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Xinwang Liu, Lei Wang, Xinzhong Zhu, Miaomiao Li, En Zhu, Tongliang Liu, Li Liu, Yong Dou, Jianping Yin
Multiple kernel learning (MKL) has been intensively studied during the past decade. It optimally combines the multiple channels of each sample to improve classification performance. However, existing MKL algorithms cannot effectively handle the situation where some channels of the samples are missing, which is not uncommon in practical applications. This paper proposes three absent MKL (AMKL) algorithms to address this issue. Different from existing approaches where missing channels are firstly imputed and then a standard MKL algorithm is deployed on the imputed data, our algorithms directly classify each sample based on its observed channels, without performing imputation...
January 28, 2019: IEEE Transactions on Pattern Analysis and Machine Intelligence
Riccardo Masetti, Salvatore N Bertuccio, Andrea Pession, Franco Locatelli
The scenario of paediatric acute myeloid leukaemia (AML), particularly non-Down syndrome acute megakaryoblastic leukaemia (non-DS-AMKL), has been recently revolutionized by the advent of large-scale, genomic sequencing technologies. In this changing landscape, a significantly relevant discovery has been represented by the identification of the CBFA2T3-GLIS2 fusion gene, which is the result of a cryptic inversion of chromosome 16. It is the most frequent chimeric oncogene identified to date in non-DS-AMKL, although it seems not to be exclusively restricted to the French-American-British M7 subgroup...
February 2019: British Journal of Haematology
Guangjie Zhao, Wanling Wu, Xiaoqin Wang, Jingwen Gu
Acute megakaryocytic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is challenging to diagnose due to frequent myelofibrosis (MF) and a low percentage of blast cells. In the present study, clinical characteristics and experimental observations in 9 adult patients diagnosed with AMKL, who were recruited by the Sino-U.S. Shanghai Leukemia Co-operative Group, were analyzed in order to summarize the diagnostic experience and provide recommendations on diagnosing AMKL. All the patients were diagnosed according to the 2008 World Health Organization diagnostic criteria...
December 2018: Oncology Letters
Cécile K Lopez, Thomas Mercher
Pediatric acute megakaryoblastic leukemia (AMKL) are generally associated with poor prognosis and the expression of fusion oncogenes involving transcriptional regulators. Recent results indicate that the ETO2-GLIS2 fusion, associated with 25-30 % of pediatric AMKL, binds and alters the activity of regulatory regions of gene expression, called "enhancers", resulting in the deregulation of GATA and ETS factors essential for the development of hematopoietic stem cells. An imbalance in GATA/ETS factor activity is also found in other AMKL subgroups...
November 2018: Médecine Sciences: M/S
Christopher J Forlenza, Yanming Zhang, JinJuan Yao, Ryma Benayed, Peter Steinherz, Kavitha Ramaswamy, Rachel Kessel, Mikhail Roshal, Neerav Shukla
Acute Megakaryoblastic leukemia (AMKL) constitutes ~5-15% of cases of non-Down syndrome AML in children, and in the majority of cases, chimeric oncogenes resulting from recurrent gene rearrangements are identified. Based upon these rearrangements several molecular subsets have been characterized providing important prognostic information. One such subset includes a group of patients with translocations involving the KMT2A gene, which has been associated with various fusion partners in patients with AMKL. Here we report the molecular findings of a 2 year old girl with AMKL and t(11;17)(q23;25) found to have a KMT2A-SEPT9 fusion identified through targeted RNA sequencing...
November 19, 2018: Cold Spring Harbor Molecular Case Studies
Jinjun Cheng, Matthew M Klairmont, John K Choi
BACKGROUND: Recent data have demonstrated the high sensitivity and specificity of peripheral blood flow cytometry (PBFC) for the diagnosis of pediatric leukemia; however, diagnostically significant immunophenotypic discrepancies between PBFC and bone marrow (BM) evaluation, which result in different lineage assignment and treatment protocols, can rarely occur. Here, we sought to further characterize the performance of PBFC for pediatric leukemia and highlight the exceptions when PBFC can result in misdiagnosis...
January 2019: Pediatric Blood & Cancer
Matthew M Klairmont, Deepthi Hoskoppal, Nour Yadak, John Kim Choi
Objectives: Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation. Methods: The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL. Results: The sensitivities of CD42b, CD61, and vWF were 90...
October 1, 2018: American Journal of Clinical Pathology
Mathieu Roussy, Mélanie Bilodeau, Loubna Jouan, Pauline Tibout, Louise Laramée, Emmanuelle Lemyre, France Léveillé, Frédérique Tihy, Sophie Cardin, Camille Sauvageau, Françoise Couture, Isabelle Louis, Aurélien Choblet, Natalie Patey, Patrick Gendron, Michel Duval, Pierre Teira, Josée Hébert, Brian T Wilhelm, John K Choi, Tanja A Gruber, Henrique Bittencourt, Sonia Cellot
The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60%-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners...
June 2018: Genes, Chromosomes & Cancer
Te Ling, John D Crispino, Maria Zingariello, Fabrizio Martelli, Anna Rita Migliaccio
GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation...
March 2018: Expert Review of Hematology
Anne-Charlotte Teyssier, Hélène Lapillonne, Marlene Pasquet, Paola Ballerini, André Baruchel, Stephane Ducassou, Odile Fenneteau, Arnaud Petit, Wendy Cuccuini, Christine Ragu, Claude Preudhomme, Thomas Mercher, Nicolas Sirvent, Guy Leverger
We report the outcome of 27 children with de novo acute megakaryoblastic leukemia (AMKL) (excluding Down syndrome) enrolled in the French multicenter prospective study ELAM02 (2005-2011). There was no difference in gender, initial leukocyte count, CNS involvement, and complete remission rate (88.9%), as compared to other acute myeloid leukemia (AML) subtypes. AMKL patients had a significantly poorer outcome (5-year overall survival 54% [CI 95% 33%-71%] than children with other AML subtypes (5-year overall survival 73% [CI 95% 68%-77%] p = 0...
November 2017: Pediatric Hematology and Oncology
Daiane Correa de Souza, Amanda Faria de Figueiredo, Daniela R Ney Garcia, Elaine Sobral da Costa, Moneeb A K Othman, Thomas Liehr, Eliana Abdelhay, Maria Luiza Macedo Silva, Teresa de Souza Fernandez
BACKGROUND: Children with Down syndrome (DS) have an enhanced risk of developing acute leukemia, with the most common subtype being acute megakaryoblastic leukemia (AMKL). Myeloid leukemia in Down syndrome (ML-DS) is considered a disease with distinct clinical and biological features. There are few studies focusing on the clonal cytogenetic changes during evolution of ML-DS. CASE PRESENTATION: Here, we describe a complex karyotype involving a previously unreported set of chromosomal abnormalities acquired during progression of ML-DS in an infant boy: derivative der(1)t(1;15)(q24;q23), translocation t(4;5)(q26;q33) and derivative der(15)t(7;15)(p21;q23)...
2017: Molecular Cytogenetics
Ting Liu, Zhenxing Zhang, Chunjie Yu, Chang Zeng, Xiaoqing Xu, Guixian Wu, Zan Huang, Wenhua Li
BACKGROUND AND PURPOSE: The poor prognosis of acute megakaryoblastic leukaemia (AMKL) means there is a need to develop novel therapeutic methods to treat this condition. It was recently shown that inducing megakaryoblasts to undergo terminal differentiation is effective as a treatment for AMKL. This encouraged us to identify a compound that induces megakaryocyte differentiation, which could then act as a potent anti-leukaemia agent. EXPERIMENTAL APPROACH: The effects of tetrandrine on the expression of CD41 and cell morphology were investigated in AMKL cells...
December 2017: British Journal of Pharmacology
Cécile K Lopez, Sébastien Malinge, Muriel Gaudry, Olivier A Bernard, Thomas Mercher
Pediatric leukemia presents specific clinical and genetic features from adult leukemia but the underpinning mechanisms of transformation are still unclear. Acute megakaryoblastic leukemia (AMKL) is the malignant accumulation of progenitors of the megakaryocyte lineage that normally produce blood platelets. AMKL is diagnosed de novo, in patients showing a poor prognosis, or in Down syndrome (DS) patients with a better prognosis. Recent data show that de novo AMKL is primarily associated with chromosomal alterations leading to the expression of fusions between transcriptional regulators...
September 2017: Trends in Cancer
Joseph B Fisher, Maureen McNulty, Michael J Burke, John D Crispino, Sridhar Rao
Acute Myeloid Leukemia (AML) is a hematologic malignancy with a poor prognosis. Recent genome-wide sequencing studies have identified frequent mutations in genes encoding members of the cohesin complex. Mutations in cohesin contribute to myeloid malignancies by conferring enhanced self-renewal of hematopoietic stem and progenitor cells but the mechanisms behind this phenotype have not been fully elucidated. Of note, cohesin mutations are highly prevalent in acute megakaryocytic leukemia associated with Down syndrome (DS-AMKL), where they occur in over half of patients...
April 2017: Trends in Cancer
Tohru Fujiwara
The development of mature blood cell from hematopoietic stem cells is regulated by transcription factors that coordinate the expression of lineage-specific genes. GATA transcription factors are zinc finger DNA-binding proteins that play crucial roles in various biological processes, including hematopoiesis. Among GATA family proteins, GATA-1, GATA-2, and GATA-3 are essential for hematopoiesis. GATA-1 functions to promote development of erythrocytes, megakaryocytes, eosinophils, and mast cells. Mutations in GATA-1 are associated with acute megakaryoblastic leukemia (AMKL), congenital erythroid hypoplasia (Diamond-Blackfan anemia; DBA), and X-linked anemia and/or thrombocytopenia...
June 2017: Tohoku Journal of Experimental Medicine
Elizabeth Margolskee, Jad Saab, Julia T Geyer, Alexander Aledo, Susan Mathew
BACKGROUND The reciprocal translocation t(1;22)(p13;q13) involving the RBM15 and MKL1 genes is an uncommon abnormality that occurs in a subset of acute myeloid leukemia with megakaryocytic differentiation (AMKL). Variant translocations have been infrequently described in this subtype of leukemia. CASE REPORT We describe the case of a 3-month-old girl who presented with progressive abdominal distension, vomiting, and fever. Although there was no morphologic evidence of leukemia in the bone marrow, cytogenetic and metaphase fluorescence in situ hybridization analysis identified an insertion of p13p31 bands of chromosome 1 onto the long arm of chromosome 22, resulting in the karyotype: 46,XX,ins(22;1)(q13;p13p31)...
April 19, 2017: American Journal of Case Reports
Verónica Ayllón, Marina Vogel-González, Federico González-Pozas, Joan Domingo-Reinés, Rosa Montes, Lucía Morales-Cacho, Verónica Ramos-Mejía
Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1, which is linked to an earlier disease onset (median of 6months of age) and arises in utero. Here we report the generation of two hPSC cell lines constitutively expressing the oncogene RBM15-MKL1, resulting in an increased expression of known RBM15-MKL1 gene targets...
March 2017: Stem Cell Research
(no author information available yet)
ETO2-GLIS2 promotes megakaryocytic identify and self-renewal to promote AMKL.
March 24, 2017: Cancer Discovery
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