CRLF2-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 KMT2A rearrangements following chemotherap...

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Main Authors: Nisha Patel, Adam Lamble, Ilan Kirsch, Haneen Shalabi, Hao-Wei Wang, Sara K. Silbert, Samantha Scanlon, Constance M Yuan, Alyssa Doverte, Jake Wellek, Raul Braylan, Mark Ahlman, Evrim B Turkbey, Sandra D Bohling, Karen M Chisholm, Murat Alp Oztek, Mike LaLoggia, Anupam Verma, Alexandra E Kovach, Brent L Wood, Kasey Leger, Nirali N. Shah
Format: Article
Language:English
Published: BMJ Publishing Group 2024-10-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/10/e009499.full
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author Nisha Patel
Adam Lamble
Ilan Kirsch
Haneen Shalabi
Hao-Wei Wang
Sara K. Silbert
Samantha Scanlon
Constance M Yuan
Alyssa Doverte
Jake Wellek
Raul Braylan
Mark Ahlman
Evrim B Turkbey
Sandra D Bohling
Karen M Chisholm
Murat Alp Oztek
Mike LaLoggia
Anupam Verma
Alexandra E Kovach
Brent L Wood
Kasey Leger
Nirali N. Shah
author_facet Nisha Patel
Adam Lamble
Ilan Kirsch
Haneen Shalabi
Hao-Wei Wang
Sara K. Silbert
Samantha Scanlon
Constance M Yuan
Alyssa Doverte
Jake Wellek
Raul Braylan
Mark Ahlman
Evrim B Turkbey
Sandra D Bohling
Karen M Chisholm
Murat Alp Oztek
Mike LaLoggia
Anupam Verma
Alexandra E Kovach
Brent L Wood
Kasey Leger
Nirali N. Shah
author_sort Nisha Patel
collection DOAJ
description 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 KMT2A 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 KMT2A rearrangements. In this report, we present two cases of adolescents with B-ALL harboring CRLF2 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 CRLF2 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.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-c7eef0e46fe34bf3a2c08de396cd97b72025-08-20T03:48:51ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-10-01121010.1136/jitc-2024-009499CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapyNisha Patel0Adam Lamble1Ilan Kirsch2Haneen Shalabi3Hao-Wei Wang4Sara K. Silbert5Samantha Scanlon6Constance M Yuan7Alyssa Doverte8Jake Wellek9Raul Braylan10Mark Ahlman11Evrim B Turkbey12Sandra D Bohling13Karen M Chisholm14Murat Alp Oztek15Mike LaLoggia16Anupam Verma17Alexandra E Kovach18Brent L Wood19Kasey Leger20Nirali N. Shah21Hematology Section, Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USADepartment of Pediatric Hematology & Oncology, University of Washington, Seattle, Washington, USAAdaptive Biotechnologies, Seattle, Washington, USANational Cancer Institute Pediatric Oncology Branch, Bethesda, Maryland, USALaboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USANational Cancer Institute Pediatric Oncology Branch, Bethesda, Maryland, USADepartment of Pediatric Hematology & Oncology, University of Washington, Seattle, Washington, USALaboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USALaboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USALaboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USAHematology Section, Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USADepartment of Radiology and Imaging, Medical College of Georgia, Augusta, Georgia, USARadiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland, USADepartment of Laboratories, Seattle Children’s Hospital, Seattle, Washington, USADepartment of Laboratories, Seattle Children’s Hospital, Seattle, Washington, USADepartment of Radiology, University of Washington, Seattle, Washington, USALake Erie College of Osteopathic Medicine, Rochester, New York, USANational Cancer Institute Pediatric Oncology Branch, Bethesda, Maryland, USAHematopathology, Department of Pathology and Laboratory Medicine, Children`s Hospital Los Angeles, Los Angeles, California, USAHematopathology, Department of Pathology and Laboratory Medicine, Children`s Hospital Los Angeles, Los Angeles, California, USADepartment of Pediatric Hematology & Oncology, University of Washington, Seattle, Washington, USANational Cancer Institute Pediatric Oncology Branch, Bethesda, Maryland, USALineage 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 KMT2A 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 KMT2A rearrangements. In this report, we present two cases of adolescents with B-ALL harboring CRLF2 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 CRLF2 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.https://jitc.bmj.com/content/12/10/e009499.full
spellingShingle Nisha Patel
Adam Lamble
Ilan Kirsch
Haneen Shalabi
Hao-Wei Wang
Sara K. Silbert
Samantha Scanlon
Constance M Yuan
Alyssa Doverte
Jake Wellek
Raul Braylan
Mark Ahlman
Evrim B Turkbey
Sandra D Bohling
Karen M Chisholm
Murat Alp Oztek
Mike LaLoggia
Anupam Verma
Alexandra E Kovach
Brent L Wood
Kasey Leger
Nirali N. Shah
CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
Journal for ImmunoTherapy of Cancer
title CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
title_full CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
title_fullStr CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
title_full_unstemmed CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
title_short CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy
title_sort crlf2 rearranged b cell all with extramedullary lineage switch to aml following cd19 targeted therapy
url https://jitc.bmj.com/content/12/10/e009499.full
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