Functional Testing of Relapsed Chronic Lymphocytic Leukemia Guides Precision Medicine and Maps Response and Resistance Mechanisms. An Index Case

Overview

Journal Haematologica

Specialty Hematology

Date 2022 Mar 3

PMID 35236056

Authors

Sigrid S Skanland

Marit Inngjerdingen

Henrik Bendiksen

Jamie York

Signe Spetalen

Ludvig A Munthe

Geir E Tjonnfjord

Affiliations

Soon will be listed here.

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References

de Weerdt I, Hofland T, de Boer R, Dobber J, Dubois J, van Nieuwenhuize D . Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment. Blood Adv. 2019; 3(17):2642-2652. PMC: 6737416. DOI: 10.1182/bloodadvances.2019000360. View

Skanland S, Mato A . Overcoming resistance to targeted therapies in chronic lymphocytic leukemia. Blood Adv. 2021; 5(1):334-343. PMC: 7805313. DOI: 10.1182/bloodadvances.2020003423. View

Ruiz S, Krupnik Y, Keating M, Chandra J, Palladino M, McConkey D . The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than bortezomib in lymphocytes from patients with chronic lymphocytic leukemia. Mol Cancer Ther. 2006; 5(7):1836-43. DOI: 10.1158/1535-7163.MCT-06-0066. View

Billard C . Apoptosis inducers in chronic lymphocytic leukemia. Oncotarget. 2014; 5(2):309-25. PMC: 3964209. DOI: 10.18632/oncotarget.1480. View

Mato A, Davids M, Sharman J, Roeker L, Kay N, Kater A . Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: "What's Past Is Prologue" (Shakespeare). Clin Cancer Res. 2021; 28(4):603-608. PMC: 9253788. DOI: 10.1158/1078-0432.CCR-21-1237. View

Skanland S . Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery. J Vis Exp. 2018; (140). PMC: 6235416. DOI: 10.3791/58386. View

Kornauth C, Pemovska T, Vladimer G, Bayer G, Bergmann M, Eder S . Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders. Cancer Discov. 2021; 12(2):372-387. PMC: 9762339. DOI: 10.1158/2159-8290.CD-21-0538. View

Suzuki K, Handa H, Chou T, Ishizawa K, Takubo T, Kase Y . Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2016; 105(4):445-452. DOI: 10.1007/s12185-016-2149-1. View

Letai A, Bhola P, Welm A . Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell. 2021; 40(1):26-35. PMC: 8752507. DOI: 10.1016/j.ccell.2021.12.004. View

10.

Lew T, Lin V, Cliff E, Blombery P, Thompson E, Handunnetti S . Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition. Blood Adv. 2021; 5(20):4054-4058. PMC: 8945613. DOI: 10.1182/bloodadvances.2021005083. View

11.

Skanland S, Cremaschi A, Bendiksen H, Hermansen J, Thimiri Govinda Raj D, Munthe L . An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL. Leukemia. 2019; 34(2):478-487. DOI: 10.1038/s41375-019-0569-7. View

12.

Hallaert D, Jaspers A, van Noesel C, van Oers M, Kater A, Eldering E . c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches. Blood. 2008; 112(13):5141-9. DOI: 10.1182/blood-2008-03-146704. View

13.

Yadav B, Pemovska T, Szwajda A, Kulesskiy E, Kontro M, Karjalainen R . Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Sci Rep. 2014; 4:5193. PMC: 4046135. DOI: 10.1038/srep05193. View

14.

Duechler M, Shehata M, Schwarzmeier J, Hoelbl A, Hilgarth M, Hubmann R . Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2. Leukemia. 2004; 19(2):260-7. DOI: 10.1038/sj.leu.2403592. View

15.

Salem A, Agarwal S, Dunbar M, Enschede S, Humerickhouse R, Wong S . Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma. J Clin Pharmacol. 2016; 57(4):484-492. DOI: 10.1002/jcph.821. View