CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues.

Blood
Xiaobing YuV Orian-Rousseau

Abstract

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients who are ineligible for intensive induction chemotherapy. However, complete remission rates with venetoclax-based therapies are hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. MRD is a result of leukemic stem cells being retained in bone marrow protective environments; activation of the CXCL12-CXCR4 pathway was shown to be relevant to this process. An important role is also played by cell adhesion molecules such as CD44, which has been shown to be crucial for the development of AML. Here we show that CD44 is involved in CXCL12 promotion of resistance to venetoclax-induced apoptosis in human AML cell lines and AML patient samples, which could be abrogated by CD44 knock down, knockout, or blocking with an anti-CD44 antibody. Split-Venus bimolecular fluorescence complementation showed that CD44 and CXCR4 physically associate at the cell membrane upon CXCL12 induction. In the venetoclax-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic stem cell core transcr...Continue Reading

References

Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Aug 21, 2001·The Journal of Investigative Dermatology·M RaisovaC C Geilen
Jun 1, 2002·Science·Lewis C Cantley
Sep 13, 2005·Cell·Laurie A BoyerRichard A Young
Sep 17, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna van RhenenGerrit Jan Schuurhuis
Aug 5, 2006·Blood·Anke C SpooJan A Burger
Sep 26, 2006·Nature Medicine·Liqing JinJohn E Dick
Jul 28, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Marina KonoplevaMichael Andreeff
Apr 27, 2011·British Journal of Haematology·Dale P CorkeryJason N Berman
Apr 24, 2015·Frontiers in Immunology·Véronique Orian-Rousseau
Jul 15, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jia-Yu YinZhao-Qun Deng
Jan 9, 2016·Cancer Research·Antonio SaccoIrene M Ghobrial
Jul 2, 2016·Immunology Letters·Tommaso PozzobonBarbara Molon
Oct 31, 2016·Experimental Hematology·Adam P DeveauJason N Berman
Jul 19, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Tiphanie PicotLydia Campos
Sep 16, 2017·Stem Cells and Development·Tiphanie PicotLydia Campos
Jun 11, 2019·American Journal of Hematology·Daniel A Pollyea
Nov 30, 2019·Best Practice & Research. Clinical Haematology·Craig T Jordan
Dec 24, 2019·Blood Advances·Daniel A PollyeaMarina Y Konopleva
Feb 8, 2020·Leukemia & Lymphoma·Curtis LachowiezMarina Konopleva
Mar 15, 2020·Cell Stem Cell·Arianna FumagalliJacco van Rheenen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Journal of Biological Regulators and Homeostatic Agents
G Kremmidiotis
Molecular and Cellular Biochemistry
Dayeon YuYong Chan Lee
Lancet
D G JacksonJ I Bell
Experimental Hematology & Oncology
Hanxiao XuAiguo Liu
© 2021 Meta ULC. All rights reserved