Project description:35 paired samples from initial diagnosis and first marrow relapse. Genes and pathways differentiating diagnosis and relapse were identified. Potential therapeutic targets were also identified. Experiment Overall Design: 35 patients with samples from initial diagnosis and first marrow relapse.
Project description:35 paired samples from initial diagnosis and first marrow relapse. Genes and pathways differentiating diagnosis and relapse were identified. Potential therapeutic targets were also identified. Keywords: paired
Project description:In high income countries 90% of the patients achieve complete remission after induction chemotherapy. However, 30-40% of these patients suffer from relapse. These patients face a dismal prognosis, as the majority (>60%) of relapsed patients die within 5 years. As a result, outcome for pediatric acute myeloid leukemia (AML) patients remains poor and has stabilized over the past 15 years. To prevent or better treat relapse of AML is the best option to improve outcome. Despite patient specific differences, most patients do respond to initial therapy. This suggests that at relapse, mechanisms are active that cause the altered response to chemotherapy. Detailed understanding of mechanisms that cause relapse remain largely elusive. To gain insight in the molecular pathways that characterize relapsed AML, we performed genome wide gene expression profiling on paired initial diagnosis and relapsed AML samples of 23 pediatric AML patients. We used pathway analysis to find which molecular pathways are involved in altered gene expression between diagnosis and relapse samples of individual AML patients. 23 paired diagnosis and relapse bone marrow or peripheral blood samples were collected and cryo-preserved. They were later thawed and processed for hybridization to Affymetrix U133 Plus 2.0 arrays.
Project description:Relapse and disease progression are the primary causes of treatment failure and subsequent mortality in children B-cell acute lymphocytic leukemia (B-ALL). At diagnosis and during treatment, the bone marrow adipose microenvironment is commonly observed in pediatric leukemia. However, the relationship between the bone marrow adipose microenvironment and disease progression is still not well understood.
Project description:The cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols. Experiment Overall Design: Diagnostic marrow samples from 99 children with NCI high risk B-precursor ALL treated on the protocol COG 1961 were analyzed. To study genetic profiles associated with early response to therapy, 82 of the total 99 patients were analyzed: 42 patients with a M1 marrow at day 7 of therapy were compared to 40 patients with a M3 marrow at day 7. To study the genes associated with long-term outcome, expression profiles of 59 (of the total 99) patients were analyzed: 28 patients who remained in complete continuous remission (CCR) for at least 4 years and 31 patients who suffered a bone marrow relapse within the first 3 years of initial diagnosis. Forty-two patients were common in both the early response and outcome analyses.
Project description:Single-cell RNA-seq analysis of primary human bone marrow immune populations isolated from B-ALL patient samples (matched diagnosis, remission and relapse), and healthy bone marrow donor samples.
Project description:Single-cell RNA-seq analysis of primary human bone marrow immune populations isolated from B-ALL patient samples (matched diagnosis, remission and relapse), and healthy bone marrow donor samples.
Project description:MicroRNAs(miRNAs) are a class of small non-coding RNAs that have been shown to play a crucial role in normal hematopoiesis and leukemogenesis. In this study, we aimed to identify key miRNAs relevant to differentiation arrest in acute myeloid leukemia (AML). Next-generation small RNA sequencing (RNA-seq) was performed on paired bone marrow samples from 5 AML patients at initial diagnosis and first complete remission (CR). Differentially expressed miRNAs (DEMs) at initial diagnosis as compared to CR were analyzed for each case.
Project description:Multiple myeloma (MM) is a hematological malignancy characterised by the clonal proliferation of abnormal plasma cells within the bone marrow (BM). Despite advances in treatment that have improved survival, the disease remains incurable. MM diagnosis requires invasive bone marrow biopsy to quantify the percentage of malignant plasma cells. In this study, the potential of extracellular vesicles (EVs) as a non-invasive liquid biopsy for MM diagnosis and staging was investigated. The proteomic content of patient-derived EVs was profiled via mass spectrometry from peripheral blood and bone marrow of 33 MM patients and 12 healthy donors. Biomarker signatures were identified using supervised machine learning to predict asymptomatic MM, progression to symptomatic MM, and relapse. The analysis identified a six-protein biomarker signature, comprising APOC1, KRT78, ALAD, S100A7, LGALS1, and CD226 forming four optimal logistic regression diagnostic MM models with predictive accuracies of >85%. The performance of the identified proteins, supports their potential as a minimally invasive EV-based liquid biopsy in MM diagnosis and monitoring.
Project description:Single-cell transcriptomics was performed to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis (n=19), during treatment (n=21) and at relapse (n=6). The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.
