scholarly journals Fulminant Acanthamoeba castellanii Encephalitis in an Ibrutinib-Treated Patient

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
Jessica W Crothers ◽  
Liangge Hsu ◽  
Francisco M Marty
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Treated Patient ◽  
Fatal Outcome ◽  
Acanthamoeba Castellanii ◽  
Lymphocytic Leukemia ◽  
Immunologic Function ◽  
Bruton Tyrosine Kinase

Abstract We report a case of fulminant Acanthamoeba castellanii encephalitis in a patient with chronic lymphocytic leukemia treated with ibrutinib. The unusually rapid neurologic decline and fatal outcome observed are probably related to alterations in immunologic function associated with inhibition of Bruton tyrosine kinase.

scholarly journals Comparison of Acalabrutinib, A Selective Bruton Tyrosine Kinase Inhibitor, with Ibrutinib in Chronic Lymphocytic Leukemia Cells

2016 ◽  
Vol 23 (14) ◽  
pp. 3734-3743 ◽  
Author(s):  
Viralkumar Patel ◽  
Kumudha Balakrishnan ◽  
Elena Bibikova ◽  
Mary Ayres ◽  
Michael J. Keating ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Bruton Tyrosine Kinase

scholarly journals Acalabrutinib in the treatment of chronic lymphocytic leukemia: a review of recent evidence

2021 ◽  
Vol 23 (2) ◽  
pp. 332-338
Author(s):  
Andrei A. Petrenko ◽  
Maria I. Kislova ◽  
Elena A. Dmitrieva ◽  
Eugene A. Nikitin
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Real Life ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Multicenter Studies ◽  
Bruton Tyrosine Kinase

Chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically with the recently developed drugs targeting the B-cell receptor (BCR) signalling pathway. Acalabrutinib, a second generation Bruton tyrosine kinase inhibitor, was approved in 2020 in Russia for the treatment of patients with CLL. Acalabrutinib was developed as a more selective Bruton tyrosine kinase inhibitor then ibrutinib. This drug is aimed at reducing the adverse events that limit the use of ibrutinib, such as atrial fibrillation and bleeding. Phase I/II multicenter studies have demonstrated the efficacy and safety of acalabrutinib monotherapy in untreated CLL patients and in patients with relapsed/refractory CLL and ibrutinib intolerance. Phase III trials, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy and a combination of acalabrutinib and obinutuzumab versus standard therapies and demonstrated improved efficacy and tolerability of acalabrutinib. A phase III trial comparing acalabrutinib and ibrutinib monotherapy (ELEVATE-RR) is ongoing. The results of this study along with real-life clinical data could determine the place of acalabrutinib in CLL treatment.

scholarly journals Releasing the brakes on BTK-targeting miRNA

Blood ◽  
2016 ◽  
Vol 128 (26) ◽  
pp. 3023-3024
Author(s):  
Matthew D. Blunt ◽  
Andrew J. Steele
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Histone Deacetylase ◽  
Hdac Inhibitors ◽  
Lymphocytic Leukemia ◽  
Hdac Inhibition ◽  
Bruton Tyrosine Kinase

In this issue of Blood, Bottoni et al demonstrate that histone deacetylase (HDAC) inhibition promotes the upregulation of microRNAs (miRNAs or miRs) which target Bruton tyrosine kinase (BTK), subsequently suppressing prosurvival signaling in chronic lymphocytic leukemia (CLL) samples, and highlight a rationale for HDAC inhibitors in combination with ibrutinib to treat patients.1

scholarly journals Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6287-6296 ◽  
Author(s):  
Sarah E. M. Herman ◽  
Amber L. Gordon ◽  
Erin Hertlein ◽  
Asha Ramanunni ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Cell Contact ◽  
Irreversible Inhibitor ◽  
Bcr Signaling ◽  
Bruton Tyrosine Kinase

Abstract B-cell receptor (BCR) signaling is aberrantly activated in chronic lymphocytic leukemia (CLL). Bruton tyrosine kinase (BTK) is essential to BCR signaling and in knockout mouse models its mutation has a relatively B cell–specific phenotype. Herein, we demonstrate that BTK protein and mRNA are significantly over expressed in CLL compared with normal B cells. Although BTK is not always constitutively active in CLL cells, BCR or CD40 signaling is accompanied by effective activation of this pathway. Using the irreversible BTK inhibitor PCI-32765, we demonstrate modest apoptosis in CLL cells that is greater than that observed in normal B cells. No influence of PCI-32765 on T-cell survival is observed. Treatment of CD40 or BCR activated CLL cells with PCI-32765 results in inhibition of BTK tyrosine phosphorylation and also effectively abrogates downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. In addition, PCI-32765 inhibits activation-induced proliferation of CLL cells in vitro, and effectively blocks survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement, and stromal cell contact. Based on these collective data, future efforts targeting BTK with the irreversible inhibitor PCI-32765 in clinical trials of CLL patients is warranted.

scholarly journals The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1182-1189 ◽  
Author(s):  
Sabine Ponader ◽  
Shih-Shih Chen ◽  
Joseph J. Buggy ◽  
Kumudha Balakrishnan ◽  
Varsha Gandhi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Cell Survival ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Bruton Tyrosine Kinase ◽  
Targeted Agent

Abstract B-cell receptor (BCR) signaling is a critical pathway in the pathogenesis of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), and can be targeted by inhibitors of BCR-associated kinases, such as Bruton tyrosine kinase (Btk). PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent for patients with B-cell malignancies, and is particularly active in patients with CLL. In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed correlative studies on specimens from patients receiving therapy with PCI-32765. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also down-regulated secretion of BCR-dependent chemokines (CCL3, CCL4) by the CLL cells, both in vitro and in vivo. In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 affected disease progression. In this model, PCI-32765 caused a transient early lymphocytosis, and profoundly inhibited CLL progression, as assessed by weight, development, and extent of hepatospenomegaly, and survival. Our data demonstrate that PCI-32765 effectively inhibits CLL cell migration and survival, possibly explaining some of the characteristic clinical activity of this new targeted agent.

scholarly journals Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

2021 ◽  
Vol 28 (1) ◽  
pp. 837-841
Author(s):  
Omar Alkharabsheh ◽  
Alhareth Alsayed ◽  
Diana M. Morlote ◽  
Amitkumar Mehta
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Case Reports ◽  
Invasive Fungal Infections ◽  
Lymphocytic Leukemia ◽  
High Morbidity ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib.

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