دورية أكاديمية
أعرض في EDS

Targeting conditioned media dependencies and FLT-3 in chronic lymphocytic leukemia.

التفاصيل البيبلوغرافية
العنوان: Targeting conditioned media dependencies and FLT-3 in chronic lymphocytic leukemia.
المؤلفون: Parvin S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Aryal A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Yin S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.; Harvard Medical School, Boston, MA., Fell GG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Davids MS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.; Harvard Medical School, Boston, MA.; Broad Institute of MIT and Harvard, Cambridge, MA., Letai A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.; Harvard Medical School, Boston, MA.
المصدر: Blood advances [Blood Adv] 2023 Oct 10; Vol. 7 (19), pp. 5877-5889.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Leukemia, Lymphocytic, Chronic, B-Cell*/pathology, Humans ; Culture Media, Conditioned/pharmacology ; fms-Like Tyrosine Kinase 3/therapeutic use ; Immunoglobulin Variable Region/genetics ; Immunoglobulin Variable Region/therapeutic use ; Signal Transduction ; Tumor Microenvironment
مستخلص: The importance of the stromal microenvironment in chronic lymphocytic leukemia (CLL) pathogenesis and drug resistance is well established. Despite recent advances in CLL therapy, identifying novel ways to disrupt interactions between CLL and its microenvironment may identify new combination partners for the drugs currently in use. To understand the role of microenvironmental factors on primary CLL cells, we took advantage of an observation that conditioned media (CM) collected from stroma was protective of CLL cells from spontaneous cell death ex vivo. The cytokine in the CM-dependent cells that most supports CLL survival in short-term ex vivo culture was CCL2. Pretreatment of CLL cells with anti-CCL2 antibody enhanced venetoclax-mediated killing. Surprisingly, we found a group of CLL samples (9/23 cases) that are less likely to undergo cell death in the absence of CM support. Functional studies revealed that CM-independent (CMI) CLL cells are less sensitive to apoptosis than conventional stroma-dependent CLL. In addition, a majority of the CMI CLL samples (80%) harbored unmutated immunoglobulin heavy-chain variable (IGHV) region. Bulk-RNA sequence analysis revealed upregulation of the focal adhesion and RAS signaling pathways in this group, along with expression of fms-like tyrosine kinase 3 (FLT3) and CD135. Treatment with FLT3 inhibitors caused a significant reduction in cell viability among CMI samples. In summary, we were able to discriminate and target 2 biologically distinct subgroups of CLL based on CM dependence with distinct microenvironmental vulnerabilities.
(© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
References: Blood. 2016 Jun 23;127(25):3215-24. (PMID: 27069256)
BMC Bioinformatics. 2018 Apr 12;19(1):135. (PMID: 29649993)
Cancer Lett. 2007 Oct 28;256(2):137-65. (PMID: 17629396)
Blood. 2000 Oct 15;96(8):2655-63. (PMID: 11023495)
Blood. 2020 Mar 5;135(10):709-711. (PMID: 32135019)
Blood. 2020 Mar 5;135(10):773-777. (PMID: 31951646)
Trends Immunol. 2013 Dec;34(12):592-601. (PMID: 23928062)
Cancer Cell. 2019 Oct 14;36(4):369-384.e13. (PMID: 31543463)
Clin Exp Metastasis. 2012 Aug;29(6):585-601. (PMID: 22484917)
Blood. 2009 Apr 30;113(18):4403-13. (PMID: 19008458)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Haematologica. 2011 Mar;96(3):408-16. (PMID: 21134984)
Blood. 2019 Jul 11;134(2):111-122. (PMID: 31023700)
Blood. 2002 Feb 1;99(3):1030-7. (PMID: 11807009)
Nat Immunol. 2012 Feb 19;13(4):412-9. (PMID: 22344248)
Stem Cells. 2006 May;24(5):1174-84. (PMID: 16410383)
Br J Haematol. 1996 Jan;92(1):97-103. (PMID: 8562418)
Leuk Lymphoma. 2012 Oct;53(10):1988-98. (PMID: 22397722)
Semin Cancer Biol. 2004 Jun;14(3):149-54. (PMID: 15246049)
Blood. 2022 Nov 17;140(20):2127-2141. (PMID: 35709339)
Eur J Haematol. 2003 May;70(5):290-5. (PMID: 12694164)
Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):E6644-53. (PMID: 26627255)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
J Immunol. 2007 Dec 1;179(11):7352-7. (PMID: 18025178)
Cancer Cell. 2006 May;9(5):351-65. (PMID: 16697956)
Cancer Chemother Pharmacol. 2013 Apr;71(4):1041-50. (PMID: 23385782)
Eur Cytokine Netw. 2008 Sep;19(3):119-22. (PMID: 18775807)
Mediterr J Hematol Infect Dis. 2012;4(1):e2012055. (PMID: 22973499)
Biol Chem. 2016 Jul 1;397(7):671-8. (PMID: 26910743)
Leuk Lymphoma. 1999 Nov;35(5-6):445-53. (PMID: 10609782)
Blood. 1996 Feb 1;87(3):1089-96. (PMID: 8562934)
Blood. 2012 Oct 25;120(17):3501-9. (PMID: 22955911)
Am J Nephrol. 2011;34(4):367-72. (PMID: 21876349)
معلومات مُعتمدة: P01 CA206978 United States CA NCI NIH HHS; R21 CA267527 United States CA NCI NIH HHS; R35 CA242427 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Culture Media, Conditioned)
EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
0 (Immunoglobulin Variable Region)
تواريخ الأحداث: Date Created: 20230710 Date Completed: 20231002 Latest Revision: 20240604
رمز التحديث: 20240604
مُعرف محوري في PubMed: PMC10558618
DOI: 10.1182/bloodadvances.2022008207
PMID: 37428863
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2022008207