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Acute lymphoblastic leukemia

Therapy-related B-cell acute lymphoblastic leukemia in adults has unique genetic profile with frequent loss of TP53 and inferior outcome

Leukemia volume 35, pages 2097–2101 (2021)Cite this article

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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 these genetic features.

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Fig. 1: Overall survival and comparison of frequencies of genetic abnormalities of prognostic significance.
Fig. 2: Distribution of mutations identified in t-B-ALL and de novo B-ALL.

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Acknowledgements

The authors would like to thank the staff of the cytogenetics and molecular diagnostics laboratories for their technical expertise.

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Authors and Affiliations

  1. 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

  2. Department of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Madelyn Burkart, Shira N. Dinner, Firas Wehbe & Jessica K. Altman

  3. 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

  4. Department of Preventive Medicine (Health and Biomedical Informatics), Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Masha Kocherginsky & Firas Wehbe

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  1. Liron Barnea Slonim
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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.

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Correspondence to Madina Sukhanova.

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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

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