High-Throughput Sequencing Using the Ion Torrent Personal Genome Machine for Clinical Evaluation of Somatic Hypermutation Status in Chronic Lymphocytic Leukemia
For patients with chronic lymphocytic leukemia, an important prognostic indicator is the somatic hypermutation status of immunoglobulin heavy chain variable region nucleic acid within the clonal cell population. Current clinical assays for this evaluation rely on Sanger sequencing and are complex, such that availability of testing for patients is limited and costly. However, advances in high-throughput sequencing provide an opportunity to improve complex clinical sequencing applications. Our goal was to determine whether high-throughput sequencing technology could reliably perform the sequencing required for somatic hypermutation analysis and improve clinical testing for chronic lymphocytic leukemia patients.
Authors: Morris AL, Colbourne T, Kirkpatrick I, Banerji V Abstract Nontraumatic chylous pleural effusions (chylothorax) and pericardial effusions (chylopericardium) are rare. They can, however, accompany intrathoracic malignancies and, most commonly, lymphomas. An association of chronic lymphocytic leukemia (cll) with chylopericardium has rarely been reported. A 68-year-old woman with cll, previously treated with single-agent fludarabine in the community, developed pleuritic chest pain and a new pericardial effusion. Computed tomography (ct) imaging of her chest revealed a large pericardial effusion with progressiv...
Conclusions: More than half the study patients received ibrutinib therapy at a submaximal dose without evidence of increased frequency of toxicities or disease progression. The rate of ibrutinib discontinuation was lower in our cohort than has been reported in other settings. Submaximal ibrutinib dosing will have to be further systematically evaluated. PMID: 31708654 [PubMed - in process]
Publication date: Available online 12 November 2019Source: Pharmacological ResearchAuthor(s): Zhuojun Liu, Jia Liu, Tianming Zhang, Mingxia Shi, Xiaofang Chen, Yun Chen, Jian YuAbstractReceptor tyrosine kinase-like orphan receptor 1 (ROR1) is an onco-embryonic antigen presented on chronic lymphocytic leukemia (CLL), but not on normal adult tissues, which promotes CLL-cell survival. Here, ROR1 was identified as a new client of Heat Shock Protein 90 (HSP90) via a mass spectrometry-based screen for ROR1-associated partners followed by co-immunoprecipitation (co-IP) analysis. A binding motif (ELHHPNIV) on ROR1 for HSP90 was re...
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in United States and has a rapidly evolving treatment paradigm. Two phase III clinical trials demonstrated that inhibition of Burton's tyrosine kinase (BTK) with ibrutinib results in extended progression free survival (PFS) as a first line agent when compared to standard chemoimmunotherapy in both young  and older patients . Similar PFS improvement has been noted in phase III trial with the first line use of B-cell lymphoma 2 (BCL2) inhibitor venetoclax .
Condition: Chronic Lymphocytic Leukemia (CLL) Intervention: Sponsor: AbbVie Not yet recruiting
Contributors : Y Perkarsky ; C M CroceSeries Type : Non-coding RNA profiling by high throughput sequencingOrganism : Homo sapiensWe analyzed small RNA sequencing data from CD5+/CD19+ B cells of a cohort of indolent and aggressive CLL patients compared with CD19+ B-cells of healthy donors.We identified tsRNA signatures in indolent and aggressive CLL vs. normal B-cells; we also found a drastic dysregulation of the expression of mature tRFs in CLL.
ConclusionsThe comprehensive analysis of clinical characteristics, immunophenotypic profiles and cytogenetic features can be helpful in differential diagnosis, especially for patients without an available non-bone marrow biopsy specimen. Universal prognostic factors may help with the early detection of high-risk patients and with stratification in risk-adapted therapy.
Supplemental New Drug Application -- submitted through FDA Real-Time Oncology Review program -- is based on positive Phase 3 data in patients aged 70 or younger RARITAN, N.J., Nov. 8, 2019 -- (Healthcare Sales &Marketing Network) -- The Janssen Pharma... Biopharmaceuticals, Oncology, FDA Janssen Pharmaceutical, Johnson &Johnson, IMBRUVICA, ibrutinib
AbstractHighly effective treatments for chronic lymphocytic leukemia (CLL) have the potential to reduce significant tumor burden to single cells and therefore require sensitive tools to assess for minimal residual disease (MRD) in bone marrow (BM) biopsies. Flow cytometry (FC) is the current gold standard for detection of MRD, but requires a specialized facility, specific antibody panels, collecting hundreds of thousands-to-millions of cells, and personnel with expertise in the analysis and interpretation of FC MRD data, which may not be feasible in many small laboratories. Dual-antibody immunohistochemistry (DA-IHC) can i...
Conditions: Lymphoid Leukemia; Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma Interventions: Drug: Copanlisib; Drug: Copanlisib Hydrochloride; Biological: Rituximab; Drug: Bendamustine; Drug: Bendamustine Hydrochloride Sponsors: University of Washington; National Cancer Institute (NCI); Bayer Not yet recruiting