<i>CRLF2</i>-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
Lineage switch (LS) refers to the immunophenotypic transformation of one leukemia lineage to another (ie, lymphoid to myeloid) with retention of baseline genetics. This phenomenon was originally observed in infants with B-lymphoblastic leukemia (B-ALL) with <i>KMT2A</i> rearrangements following chemotherapy, but is now increasingly being observed as a form of immune escape following targeted therapies among children and adults with B-ALL with and without <i>KMT2A</i> rearrangements. In this report, we present two cases of adolescents with B-ALL harboring <i>CRLF2</i> rearrangements (Philadelphia-like phenotype) who developed LS to acute myeloid leukemia following CD19 targeted therapy. To our knowledge, these are the first cases of LS to be reported in patients with <i>CRLF2</i> rearranged acute lymphoblastic leukemia. In addition to raising awareness that this genetic mutation may associate with lineage plasticity, our cases illustrate the importance of multi-modal disease surveillance in the diagnosis of LS.
Authors
- Alexandra E. Kovach (ORCID: https://orcid.org/0000-0002-6742-6749)
- Brent Lee Wood (ORCID: https://orcid.org/0000-0001-7414-3969)
- Constance M. Yuan (ORCID: https://orcid.org/0000-0002-2601-3665)
- Anupam Verma (ORCID: https://orcid.org/0000-0001-6555-7924)
- Nirali N. Shah (ORCID: https://orcid.org/0000-0002-8474-9080)
- Ilan Kirsch
- Sandra D. Bohling (ORCID: https://orcid.org/0009-0002-0422-4549)
- Samantha Scanlon (ORCID: https://orcid.org/0000-0002-1967-6276)
- Adam J. Lamble (ORCID: https://orcid.org/0000-0002-7781-2918)
- Sara K. Silbert (ORCID: https://orcid.org/0000-0002-2746-9410)
- Karen M. Chisholm (ORCID: https://orcid.org/0000-0002-1898-1252)
- Evrim Türkbey (ORCID: https://orcid.org/0000-0002-5216-3528)
- Raul C. Braylan
- Haneen Shalabi (ORCID: https://orcid.org/0000-0001-8692-8034)
- Alyssa Doverte (ORCID: https://orcid.org/0009-0001-0615-6757)
- Mark A. Ahlman (ORCID: https://orcid.org/0000-0003-3906-2084)
- Nisha Patel (ORCID: https://orcid.org/0000-0001-8061-0113)
- Kasey J. Leger (ORCID: https://orcid.org/0000-0002-7905-6714)
- Murat Alp Öztek (ORCID: https://orcid.org/0000-0002-4574-6637)
- Hao‐Wei Wang (ORCID: https://orcid.org/0000-0002-5408-9253)
- Mike LaLoggia
- Jake Wellek
Institutions
- Seattle Children's Hospital (US)
- National Institutes of Health (US)
- Children's Hospital of Los Angeles (US)
- Lake Erie College of Osteopathic Medicine (US)
- University of Washington (US)
- Augusta University (US)
- Keck Hospital of USC (US)
- Adaptive Biotechnologies (United States) (US)
- Seattle Children's Hospital (US)
- Center for Cancer and Blood Disorders (US)
- Virginia Cancer Specialists (US)
- National Cancer Institute (US)
- National Institutes of Health Clinical Center (US)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1136/jitc-2024-009499
- Citations
- 3
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- National Institutes of Health
- National Cancer Institute
- NIH Clinical Center