Integrated genomic analysis of chromosomal alterations and mutations in B-cell acute lymphoblastic leukemia reveals distinct genetic profiles at relapse
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PROVIDER: PRJNA526081 | ENA |
REPOSITORIES: ENA
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Project description:Background: The clonal basis of relapse in acute lymphoblastic leukemia (ALL) is complex and not fully understood. Methods: Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex-ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis-relapse samples from 13 B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients to identify patterns of genetic evolution that could account for the phenotypic changes associated with disease relapse. Findings: The integrative genomic analysis of aCGH, MLPA and NGS revealed that 100% of BCP-ALL patients showed at least one genetic alteration at diagnosis and relapse. In addition, there was a significant increase in the frequency of chromosomal lesions at the time of relapse (median, 6 alterations per sample) relative to that at diagnosis (median, 47 alterations) (p = 0.019). The combination of MLPA and aCGH techniques showed that IKZF1 was the most frequently deleted gene. Notably, TP53 was the most frequently mutated gene at relapse (31%). Two TP53 mutations were detected only at relapse, whereas the three others showed an increase of their mutational burden at relapse. Interpretation: Clonal evolution patterns were heterogeneous, involving acquisition, loss and maintenance of lesions at relapse. Therefore, this study confirmed that BCP-ALL is a genetically dynamic disease with distinct genetic profiles at diagnosis and relapse. The combination of the NGS, aCGH, and MLPA approaches enables better molecular characterization of the genetic profile in ALL patients during the evolution from diagnosis to relapse.
2020-08-12 | GSE128031 | GEO
Project description:Genome-wide DNA methylation profiling of relapse and relapse-free T-cell lymphoblastic lymphoma (T-LBL) samples. The Illumina 850k Human DNA methylation EPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in T-LBL samples. Samples included 21 relapse T-LBL samples, and 28 relapse-free T-LBL samples.
2020-05-04 | GSE131677 | GEO
Project description:The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis-relapse samples from 13 BCP-ALL patients to identify patterns of genetic evolution that could account for the phenotypic changes associated with disease relapse. The integrative genomic analysis of aCGH, MLPA and NGS revealed that 100% of the BCP-ALL patients showed at least one genetic alteration at diagnosis and relapse. In addition, there was a significant increase in the frequency of chromosomal lesions at the time of relapse (p = 0.019). MLPA and aCGH techniques showed that IKZF1 was the most frequently deleted gene. TP53 was the most frequently mutated gene at relapse. Two TP53 mutations were detected only at relapse, whereas the three others showed an increase in their mutational burden at relapse. Clonal evolution patterns were heterogeneous, involving the acquisition, loss and maintenance of lesions at relapse. Therefore, this study provides additional evidence that BCP-ALL is a genetically dynamic disease with distinct genetic profiles at diagnosis and relapse. Integrative NGS, aCGH and MLPA analysis enables better molecular characterization of the genetic profile in BCP-ALL patients during the evolution from diagnosis to relapse.
| S-EPMC7400270 | biostudies-literature
Project description:Epigenome analysis of relapse and relapse-free T-cell lymphoblastic lymphoma
| PRJNA544372 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE28460: Expression data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases GSE28461: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases Refer to individual Series
2011-09-22 | E-GEOD-28462 | biostudies-arrayexpress
Project description:Although the 5-year survival of childhood Acute Lymphoblastic Leukemia (ALL) exceeds 80%, a group of patients presents poor prognosis due to early relapse. To date, treatment strategies are defined by cytogenetically-based subtype categorization. However, ALL patients without chromosomal translocations associated with poor prognosis lack diagnostic markers to adjust specific therapies. DNA methylation alteration is a frequent event in cancer with high potential in diagnosis, prognosis and prediction of drug response. Hence, we aimed to characterize childhood B-ALLs without Philadelphia (BCR-ABL) and MLL translocations based on their DNA methylation profile of more than 450,000 CpG sites to improve accuracy in prognosis and treatment strategies.
2012-11-07 | GSE39141 | GEO
Project description:The development of a clinically relevant xenograft model of pediatric acute lymphoblastic leukemia, using a 4-drug treatment regimen designed to mimic pediatric remission induction therapy. Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. This study was designed to establish a preclinical model of resistance to induction therapy in childhood T-ALL to examine the emergence of drug resistance and identify novel therapies. We performed transcription profiling by array of human CD45-positive human lymphocytes from patients with acute pediatric lymphoblastic leukemia, and from xenografted NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Several different treatment regimes were used in this study (VLXD, VLXDR, VLXD2, VXL and VLXD2-ALL31) and are summarised in the protocols associated with this submission.
2013-11-01 | E-MEXP-3916 | biostudies-arrayexpress
Project description:Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. The current study used a pre-clinical model of induction therapy for pediatric ALL in NOD/SCID mice (Samuels et al Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52) to study the development of drug resistance. We performed transcription profiling by array of human CD45-positive lymphocytes from patients with acute pediatric lymphoblastic leukemia, xenografted in NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Both the primary-patient-derived and xenograft cells were analysed. The VLXD2 treatment regime is described in full in the protocols associated with this submission and in Samuels et al (Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52). This study is an extension of E-MEXP-3916.
2017-05-01 | E-MTAB-4759 | biostudies-arrayexpress
Project description:Despite high survival rates in pediatric acute lymphoblastic leukemia (ALL), relapse remains a leading cause of cancer-related death in children. Many patients suffer from adverse drug effects during treatment and other complications later in life, and would benefit from improved relapse prediction at diagnosis. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients with pediatric ALL. Somatic mutations were called using individually matched remission samples as controls, and allelic expression of the mutations in the ALL cells was assessed using RNA-sequencing. These analyses identified 29 previously known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, and 20 mutated driver genes occurred in individual samples. We detected putative non-coding mutations in regulatory regions of seven additional genes that have not been described previously in ALL. We observed an increased burden of somatic mutations at relapse. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression. In an “ancestral clone trajectory”, the major cell clone at relapse originated from a founder clone that was not detectable at diagnosis. In a “rising diagnostic clone trajectory”, a minor cell clone at diagnosis expanded to form the major cell clone at relapse. In a “persistent diagnostic clone trajectory”, the major cell clone at diagnosis persisted during treatment until relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.
2021-08-11 | GSE163634 | GEO
Project description:Identification of chromosomal deletion and duplications in childhood acute lymphoblastic leukemia with t(12;21). This study was performed to correlate clinical parameters with chromosomal aberrations by array-CGH and to identify other potential novel cancer genes involved in leukaemia. In brief, PALL-6 was a Malay male diagnosed with B-ALL, had undergone a remission but late relapse and passed away. He was assessed under medium risk. PALL-7 is a Malay male and has a medium risk assessment, and is currently in remission. PALL-8 is a Malay female and has a medium risk assessment, and is currently in remission. PALL-9 is a Chinese male and has a high risk assessment, and is currently in remission. PALL-10 is a Malay male and has a standard risk assessment, had a relapse but is currently in remission. PALL-11 was a Malay male and had a medium risk assessment, but died during transplant. array-CGH was carried out on 11 cases of childhood acute lymphoblastic leukemia with t(12;21) diagnosed by molecular and FISH techniques. Commercial male and female genomic DNA were used as the references.
2012-06-19 | E-GEOD-32897 | biostudies-arrayexpress