Insulin-like growth factor (IGF) signaling in T-cell acute lymphoblastic leukemia

Publication date: Available online 15 September 2019Source: Advances in Biological RegulationAuthor(s): Samuel Gusscott, Francesco Tamiro, Vincenzo Giambra, Andrew P. WengAbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and occupy the bone marrow compartment, thereby interfering with the production of normal blood cells. Pediatric T-ALL is curable with intensive chemotherapy, but there are significant, long-term side effects and ∼20% of patients suffer relapse for which there are limited treatment options. Adult T-ALL in contrast is largely incurable and refractory/relapsed disease is common despite multi-agent chemotherapy (5-year overall survival of ∼40%), and thus new therapeutic targets are needed.We have reported previously on the role of the insulin-like growth factor (IGF) signaling in T-ALL, and shown that it exerts potent phenotypes in both leukemia stem cell and bulk tumor cell populations. Modulators of IGF signaling may thus prove useful in improving outcomes in patients with T-ALL. In this review, we summarize the most recent findings relating to IGF signaling in T-ALL and outline therapeutic options using clinically relevant IGF signaling modulators.
Source: Advances in Biological Regulation - Category: Biology Source Type: research

Related Links:

Authors: Yu Z, Liu L, Shu Q, Li D, Wang R Abstract Leukemia stem cells (LSCs) are responsible for therapeutic failure and relapse of acute lymphoblastic leukemia. As a result of the interplay between LSCs and bone marrow mesenchymal stem cells (BM-MSCs), cancer cells may escape from chemotherapy and immune surveillance, thereby promoting leukemia progress and relapse. The present study identified that the crosstalk between LSCs and BM-MSCs may contribute to changes of immune phenotypes and expression of hematopoietic factors in BM-MSCs. Furthermore, Illumina Genome Analyzer/Hiseq 2000 identified 7 differentially ex...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual di...
Source: Frontiers in Oncology - Category: Cancer & Oncology 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
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
This study included 18 buffy coats collected from volunteer blood donors admitted to the blood transfusion service of IRCCS Bambino Gesù Pediatric Hospital after obtaining informed consent. The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014) and conducted in accordance with the ethical principles stated in the Declaration of Helsinki. Cells Lines and Cell Culture NK-92 (malignant non-Hodgkin's lymphoma), K562 (chronic myelogenous leukemia, CD19−), Jurkat (acute T cell leukemia, CD19−) Karpas 299 (Human Non-Hodgkin's Ki-positive Large Cell ...
Source: Frontiers in Immunology - Category: Allergy & Immunology 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
Lei Shang1,2 and Minjie Wei1* 1School of Pharmacy, China Medical University, Shenyang, China 2Shenyang Medical College, Shenyang, China The protein lysine methyltransferase SMYD2 has recently emerged as a new enzyme modulate gene transcription or signaling pathways, and involved into tumor progression. However, the role of SMYD2 in drug resistant is still not known. Here, we found that inhibition of SMYD2 by specific inhibitor could enhance the cell sensitivity to cisplatin (CDDP), but not paclitaxel, NVB, and VCR in non-small cell lung cancer (NSCLC). Further study showed that SMYD2 and its substrates were overex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsWhile HSCT has historically led to a survival advantage in Ph+  ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs. Introduction Available data on the incidence and outcome of invasive fungal diseases (IFD) in children treated for a hematological malignancy or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on single site, retrospective studies or on studies performed prior to the availability of newer compounds such as broad-sp...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
More News: Acute Leukemia | Acute Lymphoblastic Leukemia | Biology | Cancer | Cancer & Oncology | Chemotherapy | Insulin | Leukemia | Pediatrics | Stem Cell Therapy | Stem Cells