Therapy-related b-cell acute lymphoblastic leukemia in adults has unique genetic profile with frequent loss of tp53 and inferior outcome

Therapy-related b-cell acute lymphoblastic leukemia in adults has unique genetic profile with frequent loss of tp53 and inferior outcome


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Access through your institution Buy or subscribe It has been recognized that patients treated with cytotoxic agents for a primary malignancy, autoimmune disorder, or after solid organ


transplant are at increased risk of developing therapy-related hematopoietic neoplasms. These neoplasms include therapy-related myeloid neoplasms (MNs) and less commonly, acute lymphoblastic


leukemia (ALL). While therapy-related MNs have been well characterized and gained recognition as a distinctive high-risk entity by World Health Organization classification of hematopoietic


neoplasms [1], attention has turned to therapy-related ALL relatively recently and more studies are needed to reveal genetic markers of prognostic and therapeutic significance. Diagnostic


criteria for t-ALL cases have not been clearly defined and previous studies often grouped therapy-related B-cell ALL (t-B-ALL) with T-cell ALL and secondary ALL (defined as ALL with a prior


history of other malignancy, regardless of treatment). To the best of our knowledge, only two studies with strict inclusive criteria focused on t-B-ALL [2, 3], with other two [4, 5]


combining B-cell and T-cell ALL cases together. Confirming previously reported findings [2,3,4,5], our cohort of t-B-ALL patients showed significantly higher frequency of high-risk lymphoid


cytogenetic abnormalities, including _KMT2A_ translocations, hypodiploid, or complex karyotype. Although t(9;22)/_BCR-ABL1_ fusion was identified in both cohorts, _CRLF2_ rearrangement,


frequent in de novo _BCR-ABL1_-like B-ALL, was not noted in our t-B-ALL cohort. Some specific genetic markers associated with dismal outcome in B-ALL, i.e., haploinsufficiency of _IKZF1_ and


_TP53_, and biallelic loss of _CDKN2A/CDKN2B_ are highly overrepresented in t-B-ALL compared to de novo B-ALL. Thus, t-B-ALL should be considered as a high-risk lymphoid neoplasm based on


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local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES *


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germline variants across 12 cancer types. Nat Commun. 2015;6:10086. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS The authors would like to thank the staff of the


cytogenetics and molecular diagnostics laboratories for their technical expertise. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pathology, Northwestern University Feinberg


School of Medicine, Chicago, IL, USA Liron Barnea Slonim, Juehua Gao, Xinyan Lu, Firas Wehbe, Lawrence Jennings, Yi-Hua Chen & Madina Sukhanova * Department of Hematology and Oncology,


Northwestern University Feinberg School of Medicine, Chicago, IL, USA Madelyn Burkart, Shira N. Dinner, Firas Wehbe & Jessica K. Altman * Department of Pathology and Laboratory Medicine


and Medical Education, Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA Oluwatobi E. Odetola, Firas Wehbe & Kamran M. Mirza * Department of Preventive Medicine


(Health and Biomedical Informatics), Northwestern University Feinberg School of Medicine, Chicago, IL, USA Masha Kocherginsky & Firas Wehbe Authors * Liron Barnea Slonim View author


publications You can also search for this author inPubMed Google Scholar * Juehua Gao View author publications You can also search for this author inPubMed Google Scholar * Madelyn Burkart


View author publications You can also search for this author inPubMed Google Scholar * Oluwatobi E. Odetola View author publications You can also search for this author inPubMed Google


Scholar * Masha Kocherginsky View author publications You can also search for this author inPubMed Google Scholar * Shira N. Dinner View author publications You can also search for this


author inPubMed Google Scholar * Xinyan Lu View author publications You can also search for this author inPubMed Google Scholar * Firas Wehbe View author publications You can also search for


this author inPubMed Google Scholar * Lawrence Jennings View author publications You can also search for this author inPubMed Google Scholar * Jessica K. Altman View author publications You


can also search for this author inPubMed Google Scholar * Kamran M. Mirza View author publications You can also search for this author inPubMed Google Scholar * Yi-Hua Chen View author


publications You can also search for this author inPubMed Google Scholar * Madina Sukhanova View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS


MS undertook concept and design; LBS, JG, Y-HC, OEO, KMM, MB, SND, JKA, FW provided study materials; MS and LBS collected and assembled data; MS, LBS, JG, and MK undertook data analysis and


clinical interpretation; MS, LBS, and JG wrote the manuscript; LJ and XL reviewed the manuscript and provided constructive critics, and MS edited the article and provided final approval.


CORRESPONDING AUTHOR Correspondence to Madina Sukhanova. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION


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RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Barnea Slonim, L., Gao, J., Burkart, M. _et al._ Therapy-related B-cell acute lymphoblastic leukemia in


adults has unique genetic profile with frequent loss of _TP53_ and inferior outcome. _Leukemia_ 35, 2097–2101 (2021). https://doi.org/10.1038/s41375-020-01061-9 Download citation * Received:


21 July 2020 * Revised: 01 September 2020 * Accepted: 05 October 2020 * Published: 21 October 2020 * Issue Date: July 2021 * DOI: https://doi.org/10.1038/s41375-020-01061-9 SHARE THIS


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