Crosstalk between 14-3-3 θ and AF4 enhances MLL-AF4 activity and promotes leukemia cell proliferation

ConclusionsFrom our data we conclude that the scaffold protein 14-3-3 θ enhances the aberrant activity of the chimeric transcription factor MLL-AF4 and, therefore, represents a new player in the molecular pathogenesis of t(4;11)-positive leukemia and a new promising therapeutic target.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research

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CONCLUSIONS.—: Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1-like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1-like B-ALL is extremely complex. Ste...
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
We describe a patient with Down syndrome whose precursor B-cell acute lymphoblastic leukemia cells expressed INPP5D-ABL1 fusion gene that resulted in a reciprocal chromosome translocation t(2;9)(q27;q34). The fusion gene was present as a small subclone in the primary disease but was first identified at relapse when the subclone had expanded into a major clone. At relapse, the patient responded poorly to conventional induction chemotherapy but a transient morphologic remission was achieved after administration of imatinib monotherapy. This case demonstrates a pathway to relapse in a Down syndrome patients with acute lymphob...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
CONCLUSION: Low expression of TET2 in children with ALL is associated with poor prognosis and can be used as a molecular prognostic marker for risk group stratification. PMID: 31441600 [PubMed - as supplied by publisher]
Source: International Journal of Laboratory Hematology - Category: Hematology Authors: Tags: Int J Lab Hematol Source Type: research
Contributors : Clara Bueno ; Fernando J Calero-Nieto ; Xiaonan Wang ; Rafael Vald és-Mas ; Heleia Roca-Ho ; Francisco Gutiérrez ; Veronica Ayllon ; Pedro J Real ; David Arambilet ; Antonio Agraz-Doblás ; Ignacio Varela ; Lluis Espinosa ; Anna Bigas ; Bertie Gottgens ; Pablo Menendez ; Rolf MarschalekSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe t(4;11)(q21;q23) translocation is associated with high-risk infant pro-B-cell acute lymphoblastic leukemia (B-ALL) and arises prenatally during embryonic/fetal hematopoiesis. The developmental/pathogenic contribution ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Leukaemia is the most common childhood cancer and acute lymphoblastic leukaemia (ALL) is responsible for a third of all childhood cancer deaths. Despite the overall good prognosis, failure to eradicate the disease leads to relapse in ∼20% of patients and survival rates for infants are less than 50%. There is therefore a clear unmet need for less toxic and more effective targeted treatments. ETV6-RUNX1 translocation is the first-hit event in ∼25% of B-ALLs, initiating a clinically silent pre-leukaemia in utero.
Source: Experimental Hematology - Category: Hematology Authors: Tags: 3038 Source Type: research
Publication date: Available online 27 July 2019Source: Advances in Biological RegulationAuthor(s): Stien De Coninck, Geert Berx, Tom Taghon, Pieter Van Vlierberghe, Steven GoossensAbstractThe identification of the rare but recurrent t(2;14)(q22;q32) translocation involving the ZEB2 locus in T-cell acute lymphoblastic leukemia, suggested that ZEB2 is an oncogenic driver of this high-risk subtype of leukemia. ZEB2, a zinc finger E-box homeobox binding transcription factor, is a master regulator of cellular plasticity and its expression is correlated with poor overall survival of cancer patients. Recent loss- and gain-of-func...
Source: Advances in Biological Regulation - Category: Biology Source Type: research
In this study,TCF3 ‐HLF mRNA was detectable at a high level during induction therapy in a newly diagnosed t(17;19) ‐ALL case, whileTCF3 ‐PBX1 mRNA was undetectable at the end of induction therapy in most newly diagnosed t(1;19) ‐ALL cases. Using 4 t(17;19)‐ALL and 16 t(1;19)‐ALL cell lines, drug response profiling was analyzed. t(17;19)‐ALL cell lines were found to be significantly more resistant to vincristine (VCR), daunorubicin (DNR), and prednisolone (Pred) than t(1;19)‐ALL cell lines. Sensitivities to three (Pred, VCR, andl‐asparaginase [l‐Asp]), four (Pred, VCR,l‐Asp, and DNR) and five (Pred, VC...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Authors: Lange AP, Almeida LY, Araújo Silva CL, Scheucher PS, Chahud F, Krause A, Bohlander SK, Rego EM Abstract Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM...
Source: Brazilian Journal of Medical and Biological Research - Category: Research Tags: Braz J Med Biol Res Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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