Palbociclib promotes the antitumor activity of Venetoclax plus Azacitidine against acute myeloid leukemia

Article Hematology

Genetic diversity within leukemia-associated immunophenotype-defined subclones in AML

F. Tiso et al.

Summary: Acute myeloid leukemia is a highly heterogeneous disease, and immunophenotyping and genetic analysis can provide complementary information, which should be used together to obtain the most complete view on the disease.

ANNALS OF HEMATOLOGY (2022)

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Article Oncology

Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure

Nicholas J. Short et al.

Summary: The optimal frontline treatment regimen for treated secondary acute myeloid leukemia (ts-AML) is uncertain. The use of hypomethylating agent (HMA) plus venetoclax-based regimen followed by hematopoietic stem cell transplantation (HSCT) may improve outcomes for ts-AML patients, particularly those with a non-adverse risk karyotype.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Oncology

Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL

Felix Seyfried et al.

Summary: Targeting BCL-2 in B-cell malignancies, including precursor B-cell ALL, is a promising treatment strategy. However, the redundancy of anti-apoptotic BCL-2 family proteins may limit the efficacy of single targeting. Our study reveals the mutual substitution of BCL-XL and MCL-1 in leukemia cells and demonstrates that co-inhibition of BCL-2 and MCL-1 or BCL-XL synergistically induces apoptosis.

LEUKEMIA (2022)

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Article Cell Biology

Aberrantly expressed Wnt5a in nurse-like cells drives resistance to Venetoclax in chronic lymphocytic leukemia

Yao Guo et al.

Summary: Plasma levels of Wnt5a in chronic lymphocytic leukemia (CLL) patients are positively correlated with absolute monocyte counts, but not lymphocyte counts. Nurse-like cells (NLCs) derived from CLL patients express Wnt5a. Wnt5a-induced NF-kappa B activation in the CLL microenvironment results in resistance to venetoclax in CLL cells.

CELL DEATH DISCOVERY (2022)

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Article Hematology

Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia

Geoffrey L. Uy et al.

Summary: This study presents the results of a multicenter, open-label, phase 1/2 study of flotetuzumab in 88 adults with relapsed/refractory AML, showing clinical benefits in PIF/ER patients and encouraging evidence of activity. Flotetuzumab represents an innovative experimental approach associated with acceptable safety.

BLOOD (2021)

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Article Cell Biology

Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML

Wittawat Chantkran et al.

Summary: Over the past 50 years, there has been significant progress in the treatment of acute myeloid leukemia (AML). Fadraciclib, a novel CDK 2/9 inhibitor, shows promising efficacy in preclinical studies for AML. It induces rapid apoptosis in AML cells and demonstrates synergistic activity when combined with BCL-2 inhibitors or conventional chemotherapy agents.

CELL DEATH DISCOVERY (2021)

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Article Oncology

Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study

Erica L. Mayer et al.

Summary: The PALLAS trial investigated whether adding 2 years of palbociclib to adjuvant endocrine therapy could improve invasive disease-free survival in early-stage hormone-receptor-positive, HER2-negative breast cancer patients, but the results showed no significant benefit. The trial was then discontinued based on the lack of efficacy observed during the planned second interim analysis.

LANCET ONCOLOGY (2021)

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Article Oncology

Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myelodysplasies (GFM)

Thomas Cluzeau et al.

Summary: The combination of Eprenetapopt with AZA showed potentially higher overall response rate (ORR) and complete remission (CR) rate, as well as longer overall survival (OS) in untreated high-risk TP53m MDS and AML patients, with main treatment-related adverse events being febrile neutropenia and neurologic adverse events.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Oncology

Emerging agents and regimens for AML

Hongtao Liu

Summary: Recent advancements in AML treatment have led to expanded therapeutic options for patients through genomic and molecular research, including targeted therapies, immunotherapy, and combinations of therapeutic agents from different classes, resulting in improved survival rates.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Review Oncology

Towards precision medicine for AML

Hartmut Dohner et al.

Summary: The rapid advances in sequencing technologies have greatly improved our understanding of AML at the molecular level, leading to the development of precision medicine approaches. Challenges in this field include safely combining agents with different mechanisms of action, overcoming primary and secondary resistance, and designing future clinical trials to address these issues.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy

Dongyao Wang et al.

Summary: Patients with chronic hepatitis B often do not respond well to IFN-alpha therapy. However, sequential IL-2 therapy has shown efficacy in increasing the frequency and function of HBV-specific CD8(+) T cells, leading to improved clinical outcomes for non-responder CHB patients. This suggests a potential new therapeutic approach for refractory CHB patients.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Cell Biology

Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA

Dongyao Wang et al.

Summary: This study analyzed the immune characteristics of retest-positive patients recovered from COVID-19, finding reduced activation and lower granzyme B-producing T cells in these patients. The high expression of ID1 and low expression of IFITM10 were associated with insufficient immune cell activation and the occurrence of retest-positive cases. These findings provide insights into impaired immune function in COVID-19 and the mechanisms underlying retest-positive cases.

JOURNAL OF MOLECULAR CELL BIOLOGY (2021)

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Article Oncology

5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-Mediated Apoptosis

Sha Jin et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Venetoclax in acute myeloid leukemia - current and future directions

Curtis Lachowiez et al.

LEUKEMIA & LYMPHOMA (2020)

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Article Hematology

CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia

Johannes Schmoellerl et al.

BLOOD (2020)

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Review Oncology

The role of CDK6 in cancer

Sofie Nebenfuehr et al.

INTERNATIONAL JOURNAL OF CANCER (2020)

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Review Biochemistry & Molecular Biology

CDK6 Inhibition: A Novel Approach in AML Management

Iris Z. Uras et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Oncology

Targeting Pharmacokinetic Drug Resistance in Acute Myeloid Leukemia Cells with CDK4/6 Inhibitors

Ales Sorf et al.

CANCERS (2020)

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Article Medicine, General & Internal

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia

C. D. DiNardo et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Oncology

Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study

Andrew H. Wei et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Medicine, General & Internal

Hepatectomy promotes recurrence of liver cancer by enhancing IL-11-STAT3 signaling

Dongyao Wang et al.

EBIOMEDICINE (2019)

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Article Hematology

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia

Courtney D. DiNardo et al.

BLOOD (2019)

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Meeting Abstract Hematology

Patterns of Sensitivity Exhibited By Venetoclax-Inclusive Drug Combinations in Acute Myeloid Leukemia

Stephen E. Kurtz et al.

BLOOD (2019)

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Article Oncology

Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1

T-C Teh et al.

LEUKEMIA (2018)

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Letter Hematology

Genetic biomarkers of sensitivity and resistance to venetoclax monotherapy in patients with relapsed acute myeloid leukemia

Brenda Chyla et al.

AMERICAN JOURNAL OF HEMATOLOGY (2018)

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Article Hematology

Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia

Hidemasa Matsuo et al.

BLOOD ADVANCES (2018)

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Meeting Abstract Hematology

Biomarkers Predicting Venetoclax Sensitivity and Strategies for Venetoclax Combination Treatment

Haijiao Zhang et al.

BLOOD (2018)

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Meeting Abstract Hematology

Phase I Study of Palbociclib Alone and in Combination in Patients with Relapsed and Refractory (R/R) Leukemias

Tapan M. Kadia et al.

BLOOD (2018)

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Review Hematology

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Hartmut Doehner et al.

BLOOD (2017)

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Review Oncology

Pathways and mechanisms of venetoclax resistance

Prithviraj Bose et al.

LEUKEMIA & LYMPHOMA (2017)

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Article Oncology

Combined venetoclax and alvocidib in acute myeloid leukemia

James Bogenberger et al.

ONCOTARGET (2017)

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Article Multidisciplinary Sciences

Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia

Chengyin Min et al.

PLOS ONE (2017)

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Article Hematology

Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6

Iris Z. Uras et al.

BLOOD (2016)

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Meeting Abstract Hematology

CDK4/6 Inhibitor Palbociclib for Treatment of KMT2A-Rearranged Acute Myeloid Leukemia: Interim Analysis of the AMLSG 23-14 Trial

Stefan Froehling et al.

BLOOD (2016)

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Editorial Material Hematology

CDK6 is a regulator of stem cells Egr to wake up

Monica L. Guzman

BLOOD (2015)

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Article Hematology

International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts

Herve Dombret et al.

BLOOD (2015)

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Article Oncology

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study

Richard S. Finn et al.

LANCET ONCOLOGY (2015)

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Article Hematology

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

Ruth Scheicher et al.

BLOOD (2015)

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Article Hematology

Requirement for CDK6 in MLL-rearranged acute myeloid leukemia

Theresa Placke et al.

BLOOD (2014)

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Article Cell & Tissue Engineering

BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells

Eleni D. Lagadinou et al.

CELL STEM CELL (2013)

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Article Hematology

Concomitant inhibition of DNA methyltransferase and BCL-2 protein function synergistically induce mitochondrial apoptosis in acute myelogenous leukemia cells

Twee Tsao et al.

ANNALS OF HEMATOLOGY (2012)

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Article Oncology

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

Pierre Fenaux et al.

LANCET ONCOLOGY (2009)

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Article Hematology

Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia

Lisheng Wang et al.

BLOOD (2007)

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Article Oncology

Decitabine improves patient outcomes in myelodysplastic syndromes - Resuits of a Phase III randomized study

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CANCER (2006)

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Article Biochemistry & Molecular Biology

Novel role for JNK as a stress-activated Bcl2 kinase

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JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

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Palbociclib promotes the antitumor activity of Venetoclax plus Azacitidine against acute myeloid leukemia

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