Mutations associated with a 17-gene leukemia stem cell score and its prognostic relevance in the context of the European LeukemiaNet classification for acute myeloid leukemia.

Mutations associated with a 17-gene leukemia stem cell score and its prognostic relevance in the context of the European LeukemiaNet classification for acute myeloid leukemia. Haematologica. 2019 Aug 14;: Authors: Bill M, Nicolet D, Kohlschmidt J, Walker CJ, Mrózek K, Eisfeld AK, Papaioannou D, Rong-Mullins X, Brannan Z, Kolitz JE, Powell BL, Archer KJ, Dorrance AM, Carroll AJ, Stone RM, Byrd JC, Garzon R, Bloomfield CD, Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology Abstract Leukemia stem cells are more resistant to standard chemotherapy and their persistence during remission can cause relapse which is still one of the major clinical challenges in the treatment of acute myeloid leukemia. A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients' outcomes. We generated a previously described 17-gene expression score comprising genes differently expressed between leukemia stem cells and leukemic bulk blasts, for 934 adult patients with de novo acute myeloid leukemia, and studied associations of the 17-gene leukemia stem cell score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia. We found that patients with a high 17-gene score were older and had more mutations. The 17-gene score was found to have a prognostic impact in both younger (aged
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research

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Publication date: Available online 7 August 2019Source: The Lancet HaematologyAuthor(s): Farhad Ravandi, Rita Assi, Naval Daver, Christopher B Benton, Tapan Kadia, Philip A Thompson, Gautam Borthakur, Yesid Alvarado, Elias J Jabbour, Marina Konopleva, Koichi Takahashi, Steven Kornblau, Courtney D DiNardo, Zeev Estrov, Wilmer Flores, Sreyashi Basu, James Allison, Padmanee Sharma, Sherry Pierce, Allison PikeSummaryBackgroundOutcomes for younger patients with acute myeloid leukaemia have moderately improved over the past two decades owing to better supportive care and recent introduction of novel targeted agents. Blocking PD-...
Source: The Lancet Haematology - Category: Hematology Source Type: research
It has been demonstrated that microRNA-98 (miR-98) is dysregulated in multiple types of solid tumors, but its expression and impact in acute myeloid leukemia (AML) is unclear. To explore the prognostic role of miR-98 in AML, 164 AML patients with the miR-98 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. First, patients were divided into chemotherapy-only (chemotherapy) group and allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was then divided in two groups by the median expression level of miR-98. In chemotherapy group, high miR-98 express...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Acute myeloid leukemia (AML) is a genetically and morphologically heterogenous disease [1,2]. In The Cancer Genome Atlas project, the average number of mutations per patient was 13, and 23 significant gene mutations were frequently found with a complex interplay of genetic mutations at diagnosis [3]. Many studies have investigated the functional roles of these mutations [4-7]. For example, DNMT3A-R882H mutation is one of the most common mutations and in particular, several studies have suggested that it is likely to arise in the pre-leukemic hematopoietic stem cell compartment, that lead to inactivation of apoptosis, induc...
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
This article reviews data from several phase I、II clinical trials that evaluating PD-1 and CTLA-4 inhibitors on AML patients and discusses especially efficacy and adverse events as well as prospects of these drugs in treating acute myeloid leukemia.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Authors: Lehrnbecher T Abstract Introduction: Invasive fungal disease (IFD) is a significant cause for morbidity and mortality in children receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). As compared to adults, children may differ from adults in specific aspects regarding epidemiology, diagnosis and management of IFD. Areas covered: The review provides an overview over the epidemiology of IFD in children with cancer or undergoing HSCT, diagnostic tools, preventive and therapeutic strategies. Expert opinion: Whereas the risk for IFD is highest in children with acute myeloid leukem...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
AbstractSirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes ...
Source: Journal of Zhejiang University. Science. B. - Category: Universities & Medical Training Source Type: research
Abstract Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML)...
Source: J Zhejiang Univ Sci ... - Category: Science Authors: Tags: J Zhejiang Univ Sci B Source Type: research
Elda Pereira Noronha1†, Luísa Vieira Codeço Marques1†, Francianne Gomes Andrade1, Luiz Claudio Santos Thuler2, Eugênia Terra-Granado1, Maria S. Pombo-de-Oliveira1*† and the Brazilian Collaborative Study Group of Acute Leukemia‡ 1Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil 2Clinical Research Division, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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