Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia
A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment rem...
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| Veröffentlicht in: | Cancer cell 2020-06, Vol.37 (6), p.867-882.e12 |
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| creator | Witkowski, Matthew T. Dolgalev, Igor Evensen, Nikki A. Ma, Chao Chambers, Tiffany Roberts, Kathryn G. Sreeram, Sheetal Dai, Yuling Tikhonova, Anastasia N. Lasry, Audrey Qu, Chunxu Pei, Deqing Cheng, Cheng Robbins, Gabriel A. Pierro, Joanna Selvaraj, Shanmugapriya Mezzano, Valeria Daves, Marla Lupo, Philip J. Scheurer, Michael E. Loomis, Cynthia A. Mullighan, Charles G. Chen, Weiqiang Rabin, Karen R. Tsirigos, Aristotelis Carroll, William L. Aifantis, Iannis |
| description | A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.
[Display omitted]
•Patient B-ALL bone marrow displays extensively remodeled myeloid compartment•Monocyte abundance is predictive of pediatric and adult B-ALL patient survival•Human B-ALL promotes emergence of CD16+ non-classical monocytes ex vivo•Anti-CSF1R therapy enhances targeted treatment of Ph+ B-ALL models in vivo
Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL. |
| doi_str_mv | 10.1016/j.ccell.2020.04.015 |
| format | Article |
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[Display omitted]
•Patient B-ALL bone marrow displays extensively remodeled myeloid compartment•Monocyte abundance is predictive of pediatric and adult B-ALL patient survival•Human B-ALL promotes emergence of CD16+ non-classical monocytes ex vivo•Anti-CSF1R therapy enhances targeted treatment of Ph+ B-ALL models in vivo
Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccell.2020.04.015</identifier><identifier>PMID: 32470390</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>acute lymphoblastic leukemia ; chemotherapy ; immune microenvironment ; monocytes ; relapse ; single cell</subject><ispartof>Cancer cell, 2020-06, Vol.37 (6), p.867-882.e12</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-e7bf89b69fc1e8a1f65f7622c17576710e22c9288a6102f117413c48a497e0f23</citedby><cites>FETCH-LOGICAL-c459t-e7bf89b69fc1e8a1f65f7622c17576710e22c9288a6102f117413c48a497e0f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610820302142$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32470390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Witkowski, Matthew T.</creatorcontrib><creatorcontrib>Dolgalev, Igor</creatorcontrib><creatorcontrib>Evensen, Nikki A.</creatorcontrib><creatorcontrib>Ma, Chao</creatorcontrib><creatorcontrib>Chambers, Tiffany</creatorcontrib><creatorcontrib>Roberts, Kathryn G.</creatorcontrib><creatorcontrib>Sreeram, Sheetal</creatorcontrib><creatorcontrib>Dai, Yuling</creatorcontrib><creatorcontrib>Tikhonova, Anastasia N.</creatorcontrib><creatorcontrib>Lasry, Audrey</creatorcontrib><creatorcontrib>Qu, Chunxu</creatorcontrib><creatorcontrib>Pei, Deqing</creatorcontrib><creatorcontrib>Cheng, Cheng</creatorcontrib><creatorcontrib>Robbins, Gabriel A.</creatorcontrib><creatorcontrib>Pierro, Joanna</creatorcontrib><creatorcontrib>Selvaraj, Shanmugapriya</creatorcontrib><creatorcontrib>Mezzano, Valeria</creatorcontrib><creatorcontrib>Daves, Marla</creatorcontrib><creatorcontrib>Lupo, Philip J.</creatorcontrib><creatorcontrib>Scheurer, Michael E.</creatorcontrib><creatorcontrib>Loomis, Cynthia A.</creatorcontrib><creatorcontrib>Mullighan, Charles G.</creatorcontrib><creatorcontrib>Chen, Weiqiang</creatorcontrib><creatorcontrib>Rabin, Karen R.</creatorcontrib><creatorcontrib>Tsirigos, Aristotelis</creatorcontrib><creatorcontrib>Carroll, William L.</creatorcontrib><creatorcontrib>Aifantis, Iannis</creatorcontrib><title>Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.
[Display omitted]
•Patient B-ALL bone marrow displays extensively remodeled myeloid compartment•Monocyte abundance is predictive of pediatric and adult B-ALL patient survival•Human B-ALL promotes emergence of CD16+ non-classical monocytes ex vivo•Anti-CSF1R therapy enhances targeted treatment of Ph+ B-ALL models in vivo
Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.</description><subject>acute lymphoblastic leukemia</subject><subject>chemotherapy</subject><subject>immune microenvironment</subject><subject>monocytes</subject><subject>relapse</subject><subject>single cell</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9UU2PFCEQJUbjrqu_wMRw9NIt0HQDB03WyaqbjDExevFCGKbYYWxghO6J---lnXWjF09Uwvuoeg-h55S0lNDh1b61FsaxZYSRlvCW0P4BOqdSyKYb5PCwzn3XNwMl8gw9KWVPKosK9RiddYwL0ilyjr5d_ZwgFn8E_BlC2sLo4w1ODk87wNchzBHwR29zgnj0OcUAccI-4rd4Vb3xpZ0nwOvbcNilzWjK5C1ew_wdgjdP0SNnxgLP7t4L9PXd1ZfVh2b96f316nLdWN6rqQGxcVJtBuUsBWmoG3onBsYsFb0YBCVQZ8WkNPUS5igVnHaWS8OVAOJYd4HenHQP8ybA1tYNsxn1Iftg8q1Oxut_f6Lf6Zt01KLjS0JV4OWdQE4_ZiiTDr4s0ZoIaS6acSKpUpwuXt0JWhMpJYO7t6FEL63ovf7dil5a0YTr2kplvfh7w3vOnxoq4PUJADWno4esi_UQLWx9BjvpbfL_NfgFLlqflg</recordid><startdate>20200608</startdate><enddate>20200608</enddate><creator>Witkowski, Matthew T.</creator><creator>Dolgalev, Igor</creator><creator>Evensen, Nikki A.</creator><creator>Ma, Chao</creator><creator>Chambers, Tiffany</creator><creator>Roberts, Kathryn G.</creator><creator>Sreeram, Sheetal</creator><creator>Dai, Yuling</creator><creator>Tikhonova, Anastasia N.</creator><creator>Lasry, Audrey</creator><creator>Qu, Chunxu</creator><creator>Pei, Deqing</creator><creator>Cheng, Cheng</creator><creator>Robbins, Gabriel A.</creator><creator>Pierro, Joanna</creator><creator>Selvaraj, Shanmugapriya</creator><creator>Mezzano, Valeria</creator><creator>Daves, Marla</creator><creator>Lupo, Philip J.</creator><creator>Scheurer, Michael E.</creator><creator>Loomis, Cynthia A.</creator><creator>Mullighan, Charles G.</creator><creator>Chen, Weiqiang</creator><creator>Rabin, Karen R.</creator><creator>Tsirigos, Aristotelis</creator><creator>Carroll, William L.</creator><creator>Aifantis, Iannis</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200608</creationdate><title>Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia</title><author>Witkowski, Matthew T. ; 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The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.
[Display omitted]
•Patient B-ALL bone marrow displays extensively remodeled myeloid compartment•Monocyte abundance is predictive of pediatric and adult B-ALL patient survival•Human B-ALL promotes emergence of CD16+ non-classical monocytes ex vivo•Anti-CSF1R therapy enhances targeted treatment of Ph+ B-ALL models in vivo
Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32470390</pmid><doi>10.1016/j.ccell.2020.04.015</doi><oa>free_for_read</oa></addata></record> |
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| subjects | acute lymphoblastic leukemia chemotherapy immune microenvironment monocytes relapse single cell |
| title | Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia |
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