22,002 results match your criteria mutated patients


Implication of folate deficiency in CYP2U1 loss of function.

J Exp Med 2021 Nov 21;218(11). Epub 2021 Sep 21.

Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Pierre Bénite, France.

Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders. Understanding of their pathogenic mechanisms remains sparse, and therapeutic options are lacking. We characterized a mouse model lacking the Cyp2u1 gene, loss of which is known to be involved in a complex form of these diseases in humans. Read More

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November 2021

Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy.

Dis Model Mech 2021 Sep 21;14(9). Epub 2021 Sep 21.

Université Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay, 91190, Gif-sur-Yvette, France.

The exon-52-deleted mdx52 mouse is a critical model of Duchenne muscular dystrophy (DMD), as it features a deletion in a hotspot region of the DMD gene, frequently mutated in patients. Deletion of exon 52 impedes expression of several brain dystrophins (Dp427, Dp260 and Dp140), thus providing a key model for studying the cognitive impairment associated with DMD and testing rescuing strategies. Here, using in vivo magnetic resonance imaging and neurohistology, we found no gross brain abnormalities in mdx52 mice, suggesting that the neural dysfunctions in this model are likely at the level of brain cellular functionalities. Read More

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September 2021

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA.

Can J Gastroenterol Hepatol 2021 10;2021:9936932. Epub 2021 Sep 10.

Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China.

Background: Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA.

Methods: DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Read More

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September 2021

Evolution and progression of Barrett's oesophagus to oesophageal cancer.

Nat Rev Cancer 2021 Sep 20. Epub 2021 Sep 20.

Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK.

Cancer cells are shaped through an evolutionary process of DNA mutation, cell selection and population expansion. Early steps in this process are driven by a set of mutated driver genes and structural alterations to the genome through copy number gains or losses. Oesophageal adenocarcinoma (EAC) and the pre-invasive tissue, Barrett's oesophagus (BE), provide an ideal example in which to observe and study this evolution. Read More

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September 2021

Paired comparisons of mutational profiles before and after brachytherapy in asian uveal melanoma patients.

Sci Rep 2021 Sep 20;11(1):18594. Epub 2021 Sep 20.

Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul, 03080, South Korea.

Uveal melanoma(UM) is the most common primary intraocular malignancy in adults. However, the incidence of UM in Asia is 10 to 20 times less than in Western populations. Therefore, for the first time, we report our whole exome sequencing (WES) data analysis to discover differences in the molecular features of Asian and Western UM, and to determine the disparities between the primary tumor before brachytherapy and enucleated samples after brachytherapy. Read More

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September 2021

Association of SLC22A1 rs622342 and ATM rs11212617 polymorphisms with metformin efficacy in patients with type 2 diabetes.

Pharmacogenet Genomics 2021 Sep 20. Epub 2021 Sep 20.

Department of Endocrinology Department of Infection Control Department of Neurology, Meizhou People's Hospital, Meizhou, Guangdong Province Department of Endocrinology, Central Hospital of Shenzhen Guangming New District, Shenzhen Department of Endocrinology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, People's Republic of China.

Metformin is the first-choice oral anti-hyperglycemic drug for type 2 diabetes mellitus (T2DM) patients. There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM. Our study was to investigate the effects of the two single nucleotide polymorphisms on the efficacy of metformin in T2DM of Han nationality in Chaoshan China. Read More

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September 2021

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

J Med Genet 2021 Sep 20. Epub 2021 Sep 20.

Department of Neurology, Neurological Diseases and Brain Function Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. Read More

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September 2021

RTK-dependent inducible degradation of mutant PI3Kα drives GDC-0077 (Inavolisib) efficacy.

Cancer Discov 2021 Sep 20. Epub 2021 Sep 20.

Research, ORIC Pharmaceuticals.

PIK3CA is one of the most frequently mutated oncogenes; the p110α protein it encodes plays a central role in tumor cell proliferation. Small molecule inhibitors targeting the PI3K p110α catalytic subunit have entered clinical trials, with early-phase GDC-0077 studies showing anti-tumor activity and a manageable safety profile in patients with PIK3CA-mutant breast cancer. However, preclinical studies have shown that PI3K pathway inhibition releases negative feedback and activates receptor tyrosine kinase signaling, reengaging the pathway and attenuating drug activity. Read More

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September 2021

Reevaluating the prognostic role of BRAF mutation in colorectal cancer liver metastases.

Am J Surg 2021 Sep 8. Epub 2021 Sep 8.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Introduction: Mutations in the BRAF proto-oncogene have been shown to predict poor patient survival following curative-intent liver surgery for metastatic colorectal cancer. The aim of the present systematic review and meta-analysis is to evaluate the effect of mutated BRAF status (mutBRAF) on the overall (OS) and disease-free survival (DFS) in these patients.

Methods: A comprehensive literature search was performed for studies reporting outcomes of patients undergoing curative-intent surgery stratified by BRAF mutation status. Read More

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September 2021

Genomic evolution and the impact of SLIT2 mutation in relapsed intrahepatic cholangiocarcinoma.

Hepatology 2021 Sep 20. Epub 2021 Sep 20.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long-term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse.

Approach & Results: We conducted whole-exome sequencing (WES) of 30 paired primary and relapsed tumors from 10 patients with ICC who received curative resection. Read More

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September 2021

EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis.

Cancer Immunol Immunother 2021 Sep 20. Epub 2021 Sep 20.

Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.

Meta-analysis was performed on the Web of Science, PubMed, Embase, and Cochrane databases to evaluate the effect of epidermal growth factor receptor (EGFR) mutation status on programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors, and the association between EGFR mutation status and PD-L1 expression in non-small cell lung cancer (NSCLC) patients. Pooled effect (hazard ratio/odds ratio, HR/OR) with 95% confidence interval (CI) was calculated, and the source of heterogeneity was explored by subgroup analysis and meta-regression using Stata/SE 15.0. Read More

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September 2021

KRAS and BRAF Mutations in Stage II/III Colon Cancer: A Systematic Review and Meta-Analysis.

J Natl Cancer Inst 2021 Sep 20. Epub 2021 Sep 20.

Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy.

Background: KRAS and BRAF mutations are well-established predictive and prognostic factors in metastatic colorectal cancer, however their impact in the adjuvant setting has not yet been established.

Methods: We performed a meta-analysis of adjuvant phase III trials in patients with stage II and III colon cancer with available data on the impact of KRAS/BRAF mutations on both disease-free survival (DFS) and overall survival (OS). Trials were subgrouped based on whether adjustment for microsatellite instability (MSI) was performed and the subgroup effect was analyzed through a meta-regression. Read More

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September 2021

Circulating tumor DNA harboring the V600E mutation may predict poor outcomes of primary papillary thyroid cancer patients.

Thyroid 2021 Sep 19. Epub 2021 Sep 19.

The University of Tokyo Institute of Medical Science, 26430, Division of Molecular Pathology, Minato-ku, Tokyo, Japan;

Background: The significance of circulating tumor DNA (ctDNA) in primary papillary thyroid cancer (PTC) has yet to be well established. This study aimed to clarify whether ctDNA carrying the V600E mutation in plasma from primary PTC patients before and after surgery can predict outcomes.

Methods: Twenty-two primary PTC patients without distant metastasis, who underwent surgical resection at the University of Tokyo Hospital, were eligible for this study. Read More

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September 2021

RNF43 Pathogenic Germline Variant in a Family with Colorectal Cancer.

Clin Genet 2021 Sep 19. Epub 2021 Sep 19.

Department of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville South, SA, Australia.

The role of RNF43 as a cause of an inherited predisposition to colorectal cancer (CRC) is yet to be fully explored. This report presents our findings of two individuals with CRC from a single family carrying a likely-pathogenic inherited germline variant in RNF43. The proband (III:1) and the proband's mother (II:2) were diagnosed with mismatch repair proficient CRCs at the age of 50 years and 65 years, respectively. Read More

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September 2021

Enrichment of Double RUNX1 Mutations in Acute Leukemias of Ambiguous Lineage.

Front Oncol 2021 31;11:726637. Epub 2021 Aug 31.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. Read More

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A Four-Gene-Based Risk Score With High Prognostic Value in Gastric Cancer.

Front Oncol 2021 2;11:584213. Epub 2021 Sep 2.

Department of Gastrointestinal Surgery & Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Background: Gastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.

Materials And Methods: We extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Read More

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September 2021

Morphological Spectrum and Survival Analysis of Diffuse Midline Glioma With H3K27M Mutation.

Cureus 2021 Aug 17;13(8):e17267. Epub 2021 Aug 17.

Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, PAK.

Background Diffuse midline gliomas with the H3K27M mutation are now recognized as separate entities due to their unique molecular signature, clinical features, and adverse outcome. Objective To determine the morphological spectrum and survival rate of diffuse midline gliomas with H3K27M mutation. Material and methods This retrospective study was conducted between January 2015 and January 2021 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Read More

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Expression of oncogenic long noncoding RNA PSMG3-antisense 1 in lung squamous cell carcinoma.

Oncol Lett 2021 Nov 27;22(5):751. Epub 2021 Aug 27.

Department of Interventional Oncology, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning 110031, P.R. China.

Lung squamous cell carcinoma (LUSC) is one of the most common subtypes of lung cancer that accounts for ~50% of all lung cancer cases. Long noncoding RNA (lncRNA) PSMG3-antisense (AS) 1 has been suggested to play an important role in various types of cancer. Therefore, the aim of the present study was to investigate the role of PSMG3-AS1 using clinical specimens and data from 130 patients with LUSC. Read More

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November 2021

Pan-RAF inhibitor LY3009120 is highly synergistic with low-dose cytarabine, but not azacitidine, in acute myeloid leukemia with mutations.

Oncol Lett 2021 Nov 20;22(5):745. Epub 2021 Aug 20.

Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Alterations in oncogenes have been implicated in various types of cancer, including acute myeloid leukemia (AML). Considering that currently, there are no targeted therapies for patients with -mutated AML despite the poor outcomes, RAF may be a potential target for AML. In this study, we first analyzed the efficacy of different MAPK inhibitors in AML cell lines. Read More

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November 2021

Novel Monoclonal Antibodies and Recombined Antibodies Against Variant SARS-CoV-2.

Front Immunol 2021 30;12:715464. Epub 2021 Aug 30.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs. Read More

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Molecular and Clinical Characterization of Patients With Metastatic Castration Resistant Prostate Cancer Achieving Deep Responses to Bipolar Androgen Therapy.

Clin Genitourin Cancer 2021 Aug 16. Epub 2021 Aug 16.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.

Background: Bipolar androgen therapy (BAT) is an emerging treatment strategy for men with metastatic castration resistant prostate cancer (mCRPC) whereby serum testosterone is cycled from supraphysiologic to near-castrate levels each month. BAT has been shown to induce clinical responses in a significant proportion of patients, some of which are extreme. We explored the clinical and molecular characteristics of patients with mCRPC who achieved deep responses to BAT. Read More

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Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations.

Int J Pediatr Otorhinolaryngol 2021 Aug 5;151:110869. Epub 2021 Aug 5.

Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA. Electronic address:

Objectives: Head and neck lymphatic malformations (HNLM) are caused by gain-of-function somatic mutations in PIK3CA. Acetylsalicylic acid (ASA/aspirin) is thought to limit growth in PIK3CA-mutated neoplasms through PI3K pathway suppression. We sought to determine if ASA could be beneficial for HNLM. Read More

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Genetic profiles of subcutaneous panniculitis-like T-cell lymphoma and clinicopathological impact of HAVCR2 mutations.

Blood Adv 2021 Sep 17. Epub 2021 Sep 17.

Seoul National University Cancer Research Institute, Korea, Republic of.

Recent studies identified germline mutations in HAVCR2 (encoding TIM-3) as a genetic factor that predisposes to subcutaneous panniculitis-like T-cell lymphoma (SPTCL). However, the differences between HAVCR2-mutated (HAVCR2MUT) and HAVCR2-wild-type (HAVCR2WT) SPTCLs remain unclear. A nationwide cohort of 53 SPTCL patients diagnosed at eight Korean institutions was established. Read More

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September 2021

Histologic and Molecular Characterization of Non-Small Cell Lung Carcinoma With Discordant ROS1 Immunohistochemistry and Fluorescence In Situ Hybridization.

Appl Immunohistochem Mol Morphol 2021 Sep 16. Epub 2021 Sep 16.

University of Utah and ARUP Laboratories, Salt Lake City, UT St. Jude Childrens' Research Hospital, Memphis, TN.

Introduction: ROS1 immunohistochemical (IHC) positivity requires follow-up with confirmatory testing such as fluorescence in situ hybridization (FISH). Identifying predictive characteristics of false positive ROS1 IHC cases could aid in optimizing testing algorithms, decrease testing costs and preserve tissue.

Materials And Methods: Retrospective results were retrieved for 2054 patients with non-small cell lung carcinoma submitted to our laboratory for molecular testing. Read More

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September 2021

Targeted Mutational Analysis of Cortisol-Producing Adenomas.

J Clin Endocrinol Metab 2021 Sep 17. Epub 2021 Sep 17.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Background: Somatic gene mutations have been identified in only about half of cortisol-producing adenomas (CPA). Affected genes include PRKACA, GNAS, PRKAR1A, and CTNNB1.

Objective: To expand our understanding of the prevalence of somatic mutations in CPA from patients with overt Cushing syndrome (OCS) and "subclinical" mild autonomous cortisol excess (MACE), with an immunohistochemistry (IHC)‒guided targeted amplicon sequencing approach using formalin-fixed paraffin-embedded (FFPE) tissue. Read More

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September 2021

Association between pathogenic germline mutations in BRCA2 and ATM and tumor-infiltrating lymphocytes in primary prostate cancer.

Cancer Immunol Immunother 2021 Sep 17. Epub 2021 Sep 17.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with improved responses to immunotherapy, it is unclear whether HR mutations or HR deficiency (HRD) scores predict for increased T-cell densities in this cancer. We evaluated 17 primary prostate tumors from patients with pathogenic germline BRCA2 mutations (gBRCA2) and 21 primary prostate tumors from patients with pathogenic germline ATM (gATM) mutations, which were compared to 19 control tumors lacking HR gene mutations, as well as the TCGA prostate cancer cohort. Read More

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September 2021

TP53 and CDKN2A mutations in patients with early-stage lung squamous cell carcinoma: an analysis of the correlations and prognostic outcomes.

Ann Transl Med 2021 Aug;9(16):1330

Department of Thoracic Oncology Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.

Background: Lung squamous cell carcinoma (LUSC) is characterized by frequent mutations of tumor protein p53 (TP53) and cyclin dependent kinase inhibitor 2A (CDKN2A). However, to date, the impact of TP53/CDKN2A status on the clinical outcome of patients with early-stage LUSC is unclear.

Methods: Tissue samples from 16 early-stage, surgically resected LUSCs were analyzed by next-generation sequencing (NGS). Read More

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Co-mutations of epidermal growth factor receptor and BRAF in Chinese non-small cell lung cancer patients.

Ann Transl Med 2021 Aug;9(16):1321

Department of Thoracic Surgery, Yunnan Cancer Center, Kunming, China.

Background: Epidermal growth factor receptor (EGFR) and BRAF are 2 driver genes in non-small cell lung cancer (NSCLC) which are normally mutually exclusive. It has been previously reported that the existence of BRAF V600E in EGFR-mutated NSCLC patients could cause resistance to EGFR tyrosine kinase inhibitors (TKIs), but the influence of other BRAF actionable mutations on resistance to EGFR-TKIs has not yet been investigated. Understanding the coexistence of EGFR and BRAF actionable mutations in Chinese NSCLC patients may be essential for further treatment and prognostic prediction. Read More

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Identification and validation of a metabolism-related model and associated with tumor-infiltrating lymphocytes in p53 mutant lung adenocarcinoma patients.

Ann Transl Med 2021 Aug;9(16):1312

Department of Nursing, First Affiliated Hospital of China Medical University, Shenyang, China.

Background: The immunosuppressive tumor microenvironment produced by cancer cells is a key mechanisms of cancer immune escape. In this study, we investigated the relationship between the metabolic patterns and tumor immune environment in the TME of lung adenocarcinoma (LUAD) with the p53 mutation.

Methods: The clinical data of 495 LUAD patients was obtained from The Cancer Genome Atlas as transcriptomic and somatic mutation data. Read More

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Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia.

Leukemia 2021 Sep 16. Epub 2021 Sep 16.

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.

Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). Read More

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September 2021