Journal articleBlood Adv · April 28, 2026
In the phase 3 randomized SEQUOIA study (NCT03336333), zanubrutinib (arm A) demonstrated superior progression-free survival (PFS) compared with bendamustine-rituximab (BR; arm B) in patients with treatment-naive chronic lymphocytic leukemia/small lymphocyt ...
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Journal articleClinical Lymphoma Myeloma and Leukemia · January 1, 2026
Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) have benefited significantly over the last decade from the approval of several novel, targeted therapeutic agents, resulting in prolonged overall survival. However, an excess ...
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Journal articleTransplant Cell Ther · August 2025
Chimeric antigen receptor T-cell therapy (CAR T-cell) is a new treatment option for relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). Novel therapies including Bruton's tyrosine kinase inhibitors (BTK), covalent or noncovalent, and an in ...
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Journal articleJ Clin Oncol · March 2025
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Up ...
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Journal articleBlood Adv · February 25, 2025
The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cycli ...
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Journal articleBlood Cancer J · February 6, 2025
Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, in ...
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Journal articleBlood Adv · May 14, 2024
High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TT ...
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Journal articleBlood · April 18, 2024
A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results show ...
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Journal articleJ Natl Compr Canc Netw · April 2024
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identifi ...
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Journal articleBlood Adv · February 27, 2024
We previously reported high rates of undetectable minimal residual disease <10-4 (uMRD4) with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by 2-year ibrutinib maintenance (I-M) in treatment-naïve chronic lymphocytic leukemia ...
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Journal articleLancet · August 19, 2023
BACKGROUND: Patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma for whom treatment has failed with both Bruton tyrosine kinase (BTK) inhibitor and venetoclax have few treatment options and poor outcomes. We aime ...
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Journal articleClin Lymphoma Myeloma Leuk · July 2023
INTRODUCTION: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. MATERIALS AND METHODS: Using deidentified ...
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Journal articleAmerican journal of hematology · May 2023
Preclinical studies have shown augmented activity when combining Bruton tyrosine kinase inhibitors (BTKi) with inhibitors of mammalian target of rapamycin (mTOR) and immunomodulatory agents (IMiD). We conducted a phase 1, open-label study at five centers i ...
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Journal articleLeukemia · April 2023
This study investigated ibrutinib plus obinutuzumab in relapsed/refractory CLL, evaluating tolerability of 3 sequencing regimens as well as overall safety and efficacy. Fifty-two patients were initially randomized 1:1:1 to receive either obinutuzumab 1 mon ...
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Journal articleJ Geriatr Oncol · January 2023
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common incurable leukemia/lymphoma in the United States. Individuals with CLL are at risk for disability, frailty, and cancer-specific complications that negatively affect health-related quality ...
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Journal articleClin Lymphoma Myeloma Leuk · October 2022
CONTEXT: The Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib, was designed for high BTK specificity and minimal toxicity. SEQUOIA (NCT03336333) is a global, open-label, randomized phase 3 study in treatment-naïve patients with CLL/SLL without del(17p) ...
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Journal articleClin Lymphoma Myeloma Leuk · October 2022
CONTEXT: Ibrutinib and other Bruton-tyrosine kinase inhibitors (BTKi) have transformed treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and improved overall survival. However, cardiovascular and other non-CLL progression rel ...
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Journal articleClin Lymphoma Myeloma Leuk · October 2022
OBJECTIVE: To evaluate real-world treatment patterns and prognostic biomarker testing in Black patients with CLL enrolled in informCLL. PATIENTS AND METHODS: informCLL, a US-based, prospective, observation registry, enrolled patients who initiated FDA-appr ...
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Journal articleLancet Oncol · August 2022
BACKGROUND: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine i ...
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Journal articleJ Natl Compr Canc Netw · June 2022
The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemoth ...
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Journal articleEur J Haematol · May 2022
INTRODUCTION: Frontline treatment of hairy cell leukemia (HCL) with a single course of the purine nucleoside analog (PNA) produces a high rate of complete remission (CR) with prolonged durations. At the time of relapse, although treatment guidelines recomm ...
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Journal articleClin Cancer Res · February 15, 2022
The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to mul ...
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Journal articleLeukemia · January 2022
Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated ...
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Journal articleFront Oncol · 2022
Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients wi ...
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Journal articleBlood Adv · December 14, 2021
Phosphoinositide 3-kinase-δ (PI3Kδ) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxici ...
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Journal articleSci Rep · November 30, 2021
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to im ...
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Journal articleHaematologica · November 1, 2021
Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinic ...
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Journal articleLeukemia · October 2021
Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons. ...
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Journal articleBlood · September 9, 2021
We report long-term follow-up of the phase 1b study of venetoclax and rituximab (VenR) in patients with relapsed chronic lymphocytic leukemia (CLL), including outcomes with continuous or limited-duration therapy. Patients received venetoclax daily (200-600 ...
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Journal articleClin Cancer Res · September 1, 2021
PURPOSE: Comorbid medical conditions define a subset of patients with chronic lymphocytic leukemia (CLL) with poor outcomes. However, which comorbidities are most predictive remains understudied. EXPERIMENTAL DESIGN: We conducted a retrospective analysis f ...
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Journal articleBlood · May 20, 2021
Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in chronic lymphocytic leukemia (CLL). Umbralisib, a novel highly selective phosphatidylinositol 3-kinase δ (PI3Kδ)/CK1ε inhibitor, is active and well tolerated in CLL patients ...
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Journal articleCells · May 11, 2021
Chronic lymphocytic leukemia (CLL) is associated with physical dysfunction and low overall fitness that predicts poor survival following the commencement of treatment. However, it remains unknown whether higher fitness provides antioncogenic effects. We id ...
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Journal articleBlood · April 15, 2021
Chronic lymphocytic lymphoma (CLL) has one of the highest familial risks among cancers. Monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, has a higher prevalence (13%-18%) in families with 2 or more members with CLL compared with the general pop ...
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Journal articleLancet Haematol · April 2021
BACKGROUND: Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, ...
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Journal articleHematology Am Soc Hematol Educ Program · December 4, 2020
Despite the proven effective approach to targeting the phosphatidylinositol-3-kinase (PI3K) pathway in B-cell malignancies, the approved PI3K inhibitors idelalisib and duvelisib have been less commonly selected for patients with chronic lymphocytic leukemi ...
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Journal articleCancer Med · November 2020
Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a ...
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Journal articleBlood · September 3, 2020
Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patie ...
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Journal articleBlood Adv · August 25, 2020
Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem ce ...
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Journal articleClin Cancer Res · July 15, 2020
PURPOSE: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. EXPERIMENTAL DESIGN: ...
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Journal articleAm J Hematol · June 2020
Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical ...
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Journal articleBlood Adv · April 28, 2020
Exercise is increasingly recognized as important to cancer care. The biology of how exercise improves outcomes is not well understood, however. Studies show that exercise favorably influences the immune system in healthy individuals (neutrophils, monocytes ...
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Journal articleBr J Haematol · March 2020
Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymp ...
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Journal articleMed Mycol Case Rep · March 2020
Ibrutinib has revolutionized the treatment of chronic lymphoid malignancies. Despite its success, ibrutinib has been linked with several reports of invasive fungal infections. We present a case of CNS aspergillosis in a CLL patient on first line ibrutinib ...
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Journal articleClin Lymphoma Myeloma Leuk · March 2020
INTRODUCTION: The therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment i ...
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Journal articleJ Natl Compr Canc Netw · February 2020
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent y ...
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Journal articleLancet Haematol · August 2019
BACKGROUND: Fludarabine, cyclophosphamide, and rituximab (FCR) can improve disease-free survival for younger (age ≤65 years) fit patients with chronic lymphocytic leukaemia with mutated IGHV. However, patients with unmutated IGHV rarely have durable respon ...
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Journal articleClin Cancer Res · July 15, 2019
PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of se ...
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Journal articleBlood Adv · May 28, 2019
Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, re ...
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Journal articleBr J Haematol · February 2019
Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcome ...
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Journal articleJ Natl Compr Canc Netw · January 2019
Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs ...
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Journal articleN Engl J Med · December 27, 2018
BACKGROUND: Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evalua ...
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Journal articleAm J Hematol · November 2018
Ibrutinib demonstrated superior response rates and survival for treatment-naïve chronic lymphocytic leukemia (CLL) patients in a pivotal study that excluded patients younger than 65 (<65) and/or with chromosome 17p13 deletion (del[17p13]). We examined outc ...
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Journal articleHaematologica · September 2018
Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treat ...
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Journal articleCancer Biol Ther · July 3, 2018
Novel therapies including kinase inhibitors (KI) have led to high and durable response in patients with chronic lymphocytic leukemia (CLL), however, some patients stop therapy. This study evaluates reasons for treatment changes among CLL patients who stopp ...
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Journal articleHaematologica · May 2018
Clinical trials that led to ibrutinib's approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinuation in clinical practice have not been adequately studied ...
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Journal articleLancet Oncol · April 2018
BACKGROUND: Umbralisib (TGR-1202) is a novel next-generation inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform p110δ (PI3Kδ), which is structurally distinct from other PI3Kδ inhibitors and shows improved isoform selectivity. Umbralisib also uniquel ...
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Journal articleJAMA Oncol · March 1, 2018
IMPORTANCE: The landscape of chronic lymphocytic leukemia (CLL) treatment has changed considerably since the first reported assessment of minimal residual disease (MRD) by flow cytometry in 1992. Chemoimmunotherapy (CIT) combinations have become the standa ...
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Journal articleJ Natl Compr Canc Netw · November 2017
Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separat ...
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Journal articleAnn Oncol · May 1, 2017
BACKGROUND: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. PATIENTS AND METHODS: We conducted a multicenter, retrospective analysis of CLL patie ...
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Journal articleLancet Oncol · February 2017
BACKGROUND: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to a ...
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Journal articleLancet Haematol · September 2016
BACKGROUND: Although several consolidation strategies to prolong treatment-free survival (TFS) in chronic lymphocytic leukaemia have been investigated, most have proven either ineffective or toxic. Ofatumumab is a human type I anti-CD20 antibody approved b ...
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Journal articleLeuk Lymphoma · May 2014
Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effecti ...
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Journal articleLeuk Lymphoma · December 2013
PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-dai ...
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Journal articlePatient Prefer Adherence · 2012
Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with sign ...
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Journal articleClin Cancer Res · November 15, 2007
PURPOSE: p16(INK4a) has been appreciated as a key regulator of cell cycle progression and senescence. Cultured human mammary epithelial cells that lack p16(INK4a) activity have been shown to exhibit premalignant phenotypes, such as telomeric dysfunction, c ...
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