Journal article
CD34+CD19-CD22+ B-cell progenitors might underlie phenotypic escape in patients treated with CD19-directed therapies
- Abstract:
- CD19-directed immunotherapies have revolutionized the treatment of advanced B-ALL. Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. B-ALL patients successfully treated with CD19-directed T-cells eventually relapse, which coupled with the early onset of CD22 expression during B-cell development suggests that pre-existing CD34+CD22+CD19- (pre)-leukemic cells could represent an "early progenitor origin-related" mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19-CD22+ cells are found in diagnostic and relapsed BM samples of ~70% B-ALL patients, and their frequency increases 2-fold in B-ALL patients in CR after CD19-CAR T-cell therapy. The median of CD34+CD19-CD22+ cells before treatment was 3-fold higher in B-ALL patients who relapse after CD19-directed immunotherapy (median follow-up of 24 months). FISH analysis in flow-sorted populations and xenograft modeling revealed that CD34+CD19-CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that pre-leukemic CD34+CD19-CD22+ progenitors may underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual-targeting as a strategy to reduce CD19- relapses. The implementation of such CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of B-ALL patients during CD19-targeted therapy is encouraged.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.4MB, Terms of use)
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- Publisher copy:
- 10.1182/blood.2021014840
Authors
- Publisher:
- American Society of Hematology
- Journal:
- Blood More from this journal
- Volume:
- 140
- Issue:
- 1
- Pages:
- 38-44
- Publication date:
- 2022-04-14
- Acceptance date:
- 2022-03-13
- DOI:
- EISSN:
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1528-0020
- ISSN:
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0006-4971
- Language:
-
English
- Keywords:
- Pubs id:
-
1250812
- Local pid:
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pubs:1250812
- Deposit date:
-
2022-04-15
- ARK identifier:
Terms of use
- Copyright holder:
- American Society of Hematology
- Copyright date:
- 2022
- Rights statement:
- Copyright © 2022 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.
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