scholarly journals Modeling the evolution of ETV6-RUNX1–induced B-cell precursor acute lymphoblastic leukemia in mice

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1041-1051 ◽  
Author(s):  
Louise van der Weyden ◽  
George Giotopoulos ◽  
Alistair G. Rust ◽  
Louise S. Matheson ◽  
Frederik W. van Delft ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Mouse Model ◽  
B Cell ◽  
Insertional Mutagenesis ◽  
Fusion Gene ◽  
Single Nucleotide Polymorphism Array ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Sleeping Beauty ◽  
Cell Precursor

Abstract The t(12;21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer and is exclusively associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The translocation arises in utero and is necessary but insufficient for the development of leukemia. Single-nucleotide polymorphism array analysis of ETV6-RUNX1 patient samples has identified multiple additional genetic alterations; however, the role of these lesions in leukemogenesis remains undetermined. Moreover, murine models of ETV6-RUNX1 ALL that faithfully recapitulate the human disease are lacking. To identify novel genes that cooperate with ETV6-RUNX1 in leukemogenesis, we generated a mouse model that uses the endogenous Etv6 locus to coexpress the Etv6-RUNX1 fusion and Sleeping Beauty transposase. An insertional mutagenesis screen was performed by intercrossing these mice with those carrying a Sleeping Beauty transposon array. In contrast to previous models, a substantial proportion (20%) of the offspring developed BCP-ALL. Isolation of the transposon insertion sites identified genes known to be associated with BCP-ALL, including Ebf1 and Epor, in addition to other novel candidates. This is the first mouse model of ETV6-RUNX1 to develop BCP-ALL and provides important insight into the cooperating genetic alterations in ETV6-RUNX1 leukemia.

scholarly journals NUTM1 is a recurrent fusion gene partner in B-cell precursor acute lymphoblastic leukemia associated with increased expression of genes on chromosome band 10p12.31-12.2

Haematologica ◽  
2019 ◽  
Vol 104 (10) ◽  
pp. e455-e459 ◽  
Author(s):  
Femke M. Hormann ◽  
Alex Q. Hoogkamer ◽  
H. Berna Beverloo ◽  
Aurélie Boeree ◽  
Ilse Dingjan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Chromosome Band ◽  
Cell Precursor ◽  
Expression Of Genes

scholarly journals Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia

2020 ◽  
Vol 4 (20) ◽  
pp. 5165-5173
Author(s):  
Hiroo Ueno ◽  
Kenichi Yoshida ◽  
Yusuke Shiozawa ◽  
Yasuhito Nannya ◽  
Yuka Iijima-Yamashita ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tp53 Mutation ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Cell Precursor ◽  
Tp53 Mutations ◽  
Positive Correlations ◽  
Panel Sequencing

Abstract Recent genetic studies using high-throughput sequencing have disclosed genetic alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes have not been fully investigated. To address this, we comprehensively examined genetic alterations and their prognostic impact in a large series of pediatric B-ALL cases. We performed targeted capture sequencing in a total of 1003 pediatric patients with B-ALL from 2 Japanese cohorts. Transcriptome sequencing (n = 116) and/or array-based gene expression analysis (n = 120) were also performed in 203 (84%) of 243 patients who were not categorized into any disease subgroup by panel sequencing or routine reverse transcription polymerase chain reaction analysis for major fusions in B-ALL. Our panel sequencing identified novel recurrent mutations in 2 genes (CCND3 and CIC), and both had positive correlations with ETV6-RUNX1 and hypodiploid ALL, respectively. In addition, positive correlations were also newly reported between TCF3-PBX1 ALL with PHF6 mutations. In multivariate Cox proportional hazards regression models for overall survival, TP53 mutation/deletion, hypodiploid, and MEF2D fusions were selected in both cohorts. For TP53 mutations, the negative effect on overall survival was confirmed in an independent external cohort (n = 466). TP53 mutation was frequently found in IGH-DUX4 (5 of 57 [9%]) ALL, with 4 cases having 17p LOH and negatively affecting overall survival therein, whereas TP53 mutation was not associated with poor outcomes among NCI (National Cancer Institute) standard risk (SR) patients. A conventional treatment approach might be enough, and further treatment intensification might not be necessary, for patients with TP53 mutations if they are categorized into NCI SR.

scholarly journals PAX5-AUTS2: A recurrent fusion gene in childhood B-cell precursor acute lymphoblastic leukemia

2012 ◽  
Vol 36 (8) ◽  
pp. e178-e181 ◽  
Author(s):  
Dagmar Denk ◽  
Karin Nebral ◽  
Jutta Bradtke ◽  
Gertrud Pass ◽  
Anja Möricke ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor

scholarly journals Novel MEIS1-FOXO1 Fusion Gene in a Case of Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5283-5283
Author(s):  
Chuang Jiang ◽  
Jiabi Qian ◽  
Wenge Hao ◽  
Wei LIU ◽  
Shuhong Shen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Functional Study ◽  
Cell Precursor ◽  
Foxo1 Gene

Abstract Background: Thanks to the total therapy and systemic basic-translation research, the overall survival rate in children with acute lymphoblastic leukemia (ALL) has dramatically improved to almost 90% over these past few decades. FOXO1 gene belongs to the forkhead family of transcription factors, which play roles in myogenic growth and differentiation. Translocation of FOXO1 with PAX3 has been reported in pediatric alveolar rhabdomyosarcoma. In B-cell precursor ALL, two cases with FOXO1 fusions have been identified already, while its function on ALL remains unknown. Here, we report a novel MEIS1-FOXO1 fusion gene in a case with B-ALL. Methods: Flowcytometery, karyotype, RT-PCR and fluorescence in were employed, MEIS1-FOXO1 was identified as novel fusion gene in a case of pediatric BCP-ALL. Using IL-3 dependent BaF3 cells as study model to test the leukemia transformation potential of MEIS1-FOXO1. Results: A novel MEIS1-FOXO1 fusion was identified in one cease of pediatric B-ALL. Panel next generation sequencing (NGS) showed that the leukemia clone had concurrent NRASG12D, TP53R273H, WHSC1E1099K, ABCC1R1166X, PHGR1H37P, HOXA3P219L and DSTP4606L somatic mutation. This patient was enrolled in CCCG-ALL2015 clinical trial (ChiCTR-IPR-14005706) and achieved completed remission and low minimal residual disease (MRD) level (MRD<0.01%) at day 19 from induction therapy. Functional study showed that MEIS1-FOXO1 fusion gene can potentiate BaF3 cells growth independent of IL3 supplement, as compared to those without MEIS1-FOXO1 fusion transduction. In the meanwhile, we have found that MEIS1-FOXO1 fusion gene can drive cells into S-phase with concurrent decreased G0/G1 phase, which might be its oncogenic role in leukemogenesis. Using qPCR methods, we have found that MEIS1-FOXO1 fusion gene altered the cell cycle related genes expression. Conclusions: Integrating the FOXO1-fusion reports, our data have added more evidence to underline the role of FOXO1 deregulation in the pathogenesis of acute lymphoblastic leukemia. Novel fusion of MEIS1-FOXO1 can potentiate B-ALL via cell cycle entry. Detailed mechanisms involved into the MEIS1-FOXO1 should be further investigated. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1569 ◽  
Author(s):  
Jan Starý ◽  
Jan Zuna ◽  
Marketa Zaliova
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Stratification ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Treatment Modalities ◽  
Routine Practice ◽  
Cell Precursor ◽  
Genetic Classification ◽  
Genomic Studies

Traditionally, genetic abnormalities detected by conventional karyotyping, fluorescencein situhybridization, and polymerase chain reaction divided childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) into well-established genetic subtypes. This genetic classification has been prognostically relevant and thus used for the risk stratification of therapy. Recently, the introduction of genome-wide approaches, including massive parallel sequencing methods (whole-genome, -exome, and -transcriptome sequencing), enabled extensive genomic studies which, together with gene expression profiling, largely expanded our understanding of leukemia pathogenesis and its heterogeneity. Novel BCP-ALL subtypes have been described. Exact identification of recurrent genetic alterations and their combinations facilitates more precise risk stratification of patients. Discovery of targetable lesions in subsets of patients enables the introduction of new treatment modalities into clinical practice and stimulates the transfer of modern methods from research laboratories to routine practice.

Single-Cell Phospho-Profiling in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia Reveals Signaling Differences in Cytogenetic and Prognostic Subgroups.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2653-2653
Author(s):  
Manon Queudeville ◽  
Sarah M. Eckhoff ◽  
Klaus-Michael Debatin ◽  
Lueder H. Meyer
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Single Cell ◽  
Poor Prognosis ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Cytogenetic Aberrations

Abstract Abstract 2653 Poster Board II-629 Oncogenesis and tumor progression are supported by alterations in cellular signaling. We used phospho-specific antibodies in combination with surface staining in flow cytometry to analyze specific signaling profiles of leukemia cells at a single cell level. We anayzed 22 xenograft samples derived from NOD/SCID-mice transplanted with primary pediatric B- cell precursor acute lymphoblastic leukemia (BCP- ALL) cells. The cells were isolated from the spleens of leukemia bearing mice and stimulated ex vivo in vitro with different stimulants and cytokines. Activation of various phosphoepitopes was analyzed by flow cytometry and compared to the basal state of unstimulated samples. TEL/AML1 fusion and MLL-rearrangements are the most common cytogenetic aberrations in childhood BCP- ALL and are associated with a good or very poor prognosis, respectively. Although there were no differences detectable in basal phosphorylation between the different cytogenetic subgroups, TEL/AML1- positive samples (n= 5) displayed a significantly lower phosphorylation of extracellular regulated kinase (ERK1/2) after stimulation with PMA (Phorbol-12-myristat-13-acetate, activator of protein kinase C) or interleukin 7 (IL-7), while they showed a significantly higher activation of p38 after stimulation with PMA, compared to samples without translocation (n= 13). Additionally, the fusion gene negative samples showed a downregulation of STAT1-phosphorylation after stimulation with interleukin 10 (IL-10) whereas the TEL/AML1-positive samples showed no change. Interestingly, the MLL- positive samples (n= 3) also did not show a difference in STAT1-phosphorylation after IL-10, but showed significantly stronger STAT1 activation in response to interferon alpha (IFN-a) compared to samples without fusion genes. Moreover, the MLL- positive samples also displayed a weaker reaction in ERK-phosphorylation after IL-7 compared to the leukemia samples without cytogenetic aberrations. Differences in other prognostic subgroups analysed include a weaker phosphorylation of p38 and JNK after anisomycin in samples where the patient initially presented with hyperleucocytosis (> 100.000 WBC/μl) (n= 3), an indicator of poor prognosis. A decrease in STAT3- activation after IL-10 was observed in samples where the patients displayed bone marrow remission on day 15 of therapy (n= 8), compared to no change in the samples of patients with > 5% residual blasts (n= 8), indicative of therapy resistance, at this timepoint. Similar to the results for the cytogenetic subgroups, there were no differences detectable at basal phosphorylation levels between the prognostic subgroups. Taken together, these data show that basal phosphorylation states of specific signaling molecules do not discriminate between the different prognostic subgroups of BCP- ALL analyzed. Cytogenetic and other prognostic subgroups however display specific profiles of signaling networks after stimulation. This strategy will prove helpful to identify mechanisms by which different subgroups with distinct clinical outcomes interpret environmental signals and hereby define pathways important for continued survival, proliferation and resistance eventually leading to novel biomarkers and targeted therapies. Disclosures: No relevant conflicts of interest to declare.

The NOD/SCID Xenograft Model Provides Clinically-Relevant Insights Into Glucocorticoid-Induced Gene Expression In Childhood B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2493-2493
Author(s):  
Vivek A Bhadri ◽  
Mark J Cowley ◽  
Warren Kaplan ◽  
Richard B Lock
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Model ◽  
B Cell ◽  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Lymphoblastic Leukemia ◽  
Xenograft Model ◽  
Differentially Expressed ◽  
Cell Precursor

Abstract Abstract 2493 Introduction. Glucocorticoids (GC) such as prednisolone (Pred) and dexamethasone (Dex) are critical drugs in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL). The NOD/SCID ALL xenograft mouse model is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report the results of a study evaluating the NOD/SCID xenograft model to investigate GC-induced gene expression. Methods. Cells from a GC-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. Engraftment, defined as the proportion of human vs mouse CD45+ cells in the peripheral blood, was monitored by serial weekly tail-vein sampling. When engraftment levels reached >50%, the mice were randomised and treated with either dexamethasone 15 mg/kg or vehicle control by intraperitoneal injection, and harvested at 0, 8, 24 or 48 h thereafter. The 48 hour groups received a second dose of vehicle or Dex at 24 hours. At the defined timepoints, the mice were euthanized and lymphoblasts harvested from the spleen. RNA was extracted, amplified and hybridised onto Illumina WG-6 V3 chips. The data was pre-processed using variance-stabilisation transformation, and quantile normalisation. Differential expression was determined using limma by comparing all treated groups to time 0, with the positive False Discovery Rate correction for multiple testing. Hierarchical clustering was used to compare groups to each other. The stability of results when reducing the number of replicates was assessed using the Recovery Score method. Functional analysis was performed using gene set enrichment analysis (GSEA) and comparison to publicly available microarray data using parametric GSEA. Results. The 8 hour Dex-treated timepoint had the most number of significantly differentially expressed genes (see Table), with fewer observed at the 24 and 48 hour Dex-treated timepoints. There was minimal significant differential gene expression across the time-matched controls. At the 8 hour timepoint, ZBTB16, a known GC-induced gene, was the most significantly upregulated gene. Other significantly differentially expressed genes included TSC22D3 and SOCS1, both downstream targets of the glucocorticoid receptor (upregulated), and BCL-2 and C-MYC (downregulated). GSEA at 8 hours revealed a significant upregulation of catabolic pathways and downregulation of pathways associated with cell proliferation, particularly C-MYC. GSEA at 24 hours revealed enrichment of pathways associated with NF-kB. Replicate analysis revealed that at the 8 hour Dex treated timepoint, a dataset with high signal and differential expression, using data from 3 replicates instead of 4 resulted in excellent recovery scores of >0.9. However at other timepoints with less signal very poor recovery scores were obtained using 3 replicates. We compared our data to publicly available datasets of GC-induced genes in ALL (Schmidt et al, Blood 2006; Rainer et al, Leukemia 2009) using parametric GSEA, which revealed that the 8 hour gene expression data obtained from the NOD/SCID xenograft model clustered with data from primary patient samples (Schmidt) rather than the cell line data (Rainer). The 24 and 48 hour datasets clustered separately from all other datasets by this method, reflecting fewer and predominantly downregulated gene expression at these timepoints. Conclusions: The NOD/SCID xenograft mouse model provides a reproducible experimental model system in which to investigate clinically-relevant mechanisms of GC-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Jianfeng Li ◽  
Yuting Dai ◽  
Liang Wu ◽  
Ming Zhang ◽  
Wen Ouyang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Molecular Subtypes ◽  
Lymphoblastic Leukemia ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Gene Expression Patterns ◽  
Cell Precursor

AbstractB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

scholarly journals Intrachromosomal Amplification of Chromosome 21 in Childhood Acute Lymphoblastic Leukemia: Study of 3 Cases

2021 ◽  
pp. 592-598
Author(s):  
Aleksandra Mroczkowska ◽  
Monika Lejman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Single Nucleotide Polymorphism Array ◽  
Lymphoblastic Leukemia ◽  
Chromosome 21 ◽  
Genetic Diagnostics ◽  
Cell Precursor ◽  
Childhood All ◽  
Fish Method

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. The presence or absence of a characteristic genetic abnormality usually observed in childhood ALL plays a very important role in determining the prognosis and stratification for treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) is an uncommon high-risk chromosomal abnormality than can occur only in 2% of childhood B-cell precursor lymphoblastic leukemia. Molecular genetic analysis and the fluorescence in situ hybridization (FISH) technique are the basic methods used to detect the presence of the most common genetic abnormalities, the presence or absence of which has an impact on the patient’s classification into the appropriate risk group. This work presents 3 BCP-ALL iAMP21-positive patients who were detected during routine genetic diagnostics using the FISH method and microarray test. iAMP21 is associated with a poor prognosis and high risk for relapse. Children with B-cell precursor lymphoblastic leukemia with this genetic entity are associated with a delayed treatment response. The FISH method and single-nucleotide polymorphism array provides a useful method to detect characteristic genetic changes.

scholarly journals Genomic Characterization of Paired Diagnosis and Relapse Samples from Adult Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5281-5281
Author(s):  
Jordi Ribera ◽  
Mar Mallo ◽  
Lurdes Zamora ◽  
Neus Solanes ◽  
Susana Vives ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
The Other ◽  
Recurrent Event ◽  
Cell Precursor ◽  
Dismal Prognosis

Abstract Background & Objective: Acute Lymphoblastic Leukemia (ALL) is an aggressive neoplasia characterized by a high genetic heterogeneity both at diagnosis and at relapse. Due to the high incidence of relapse in adults and the dismal prognosis beyond recurrence, diagnosis and relapse samples of adult ALL patients were carefully analyzed in order to identify genetic alterations related with drug resistance and disease progression. Patients & Methods: Paired diagnosis-relapse bone marrow samples from 5 adult B-cell precursor ALL (B-ALL) patients were analyzed (Ph+ ALL [n=2], normal karyotype [n=1], t(1;19)(q23;p13) [n=1] and t(8;13)(p21-22;q12) [n=1]). Copy Number Alterations (CNA) were studied with Multiplex Ligation-dependent Probe Amplification (MLPA, kits P-335 and P-202 from MRC-Holland, Amsterdam, Netherlands) and Affymetrix CytoScan HD arrays (Affymetrix, Santa Clara, USA). In the array analyses, only the CNA that encompassed at least 25 markers were considered significant. Results: Regarding karyotype, 2 patients (1 Ph+ and 1 t(1;19) at diagnosis) showed the same chromosomal translocations within a complex karyotype at relapse. On the contrary, the other Ph+ patient showed a normal karyotype at relapse, while 2 patients did not experience any karyotypic change. Regarding immunophenotype, 3/5 patients showed changes on antigen expression from diagnosis to relapse such as expression of markers of immaturity (CD34, TdT positivity and CD38 negativity), loss of lymphoid markers (CD20 and CD22) and/or acquisition of myeloid markers (CD33 and CD66c). Concerning CNA, all relapse samples were genetically related to the diagnosis clone (common clonal origin). All relapsed populations lost CNA detected at diagnosis and/or acquired new CNA but retained some of the CNA showed at diagnosis revealing clonal evolution from ancestral clones. CNA in B-ALL key genes involved in lymphoid development (IKZF1, PAX5, EBF1,VPREB1 and BLNK), proliferation (CDKN2A/B, RB1, CRLF2, C-MYC and ERG), apoptosis (BTG1, TP53 and ATM), hematopoiesis transcription factors (ETV6 and MLL) and histone modifications (KDM6A) were detected, among others. Losses in 9p were the most recurrent event both at diagnosis and at relapse. CDKN2A/B deletions were observed in all relapse samples (3/5 in homozygosis) while PAX5 deletions were present in 4/5 relapsed cases. Interestingly, all relapse samples showed CNA favoring the activation and/or the transcription of proteins involved in the Akt/C-MYC signaling pathway. Another common feature (4/5 patients) were CNA affecting genes involved in drug transport such as several ABC transporter genes and genes related to drug resistance such as PRKDC and RUNX1T1 (in 3/4 of the cases, the CNA appeared exclusively at relapse or were already present at diagnosis and increased their frequency at relapse). CNA in genes that may confer stem cell characteristics (EGR1 and USP16) were another recurrent event at relapse (3/5 samples, 2 of them were not present at diagnosis). CNA affecting the X/Y PAR1 region (CRLF2, CSF2RA and IL3RA) or VPREB1 at 22q11.22 were detected in 3/5 relapse samples, respectively. An important apoptosis cluster at 11q21q24.2 (BIRC2/3, CASP1/4/5/12, hsa-miR-34b/c, ATM and BTG4) was lost in 2/5 relapse samples (one of them was not detected at diagnosis and the other increased its frequency at relapse). Finally, ETV6 deletion (12p13.2) and duplication of Xq26.2q28 (containing ABCD1, BCAP31 and genes coding for several cancer/testis antigens) were observed in 2 relapse samples. Conclusions: SNP arrays analysis of paired B-cell precursor ALL samples at diagnosis and at relapse allows the identification of genetic alterations potentially related with ALL progression. The systematic analysis of relapse samples could contribute to the identification of specific genetic targets with potential therapeutic impact for each patient (personalized medicine). Disclosures Martínez-López: Novartis: Honoraria, Speakers Bureau. Sole:Celgene: Membership on an entity's Board of Directors or advisory committees.

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