CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy

Sara K. Silbert; Samantha Scanlon; Hao Wei Wang; Constance M. Yuan; Alyssa Doverte; Jake Wellek; Nisha Patel; Raul Braylan; Mark Ahlman; Evrim B. Turkbey; Sandra D. Bohling; Karen M. Chisholm; Murat Alp Oztek; Mike Laloggia; Anupam Verma; Haneen Shalabi; Alexandra E. Kovach; Brent L. Wood; Adam Lamble; Ilan Kirsch; Kasey Leger; Nirali N. Shah

doi:10.1136/jitc-2024-009499

CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy

Sara K. Silbert, Samantha Scanlon, Hao Wei Wang, Constance M. Yuan, Alyssa Doverte, Jake Wellek, Nisha Patel, Raul Braylan, Mark Ahlman, Evrim B. Turkbey, Sandra D. Bohling, Karen M. Chisholm, Murat Alp Oztek, Mike Laloggia, Anupam Verma, Haneen Shalabi, Alexandra E. Kovach, Brent L. Wood, Adam Lamble, Ilan KirschKasey Leger^*, Nirali N. Shah^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	e009499
Journal	Journal for immunotherapy of cancer
Volume	12
Issue number	10
DOIs	https://doi.org/10.1136/jitc-2024-009499
State	Published - Oct 26 2024

Funding

This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and the Warren Grant Magnuson Clinical Center (ZIA BC011823, NS).

Keywords

Chimeric antigen receptor - CAR
Immunotherapy
Leukemia
Next generation sequencing - NGS

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/jitc-2024-009499

Cite this

Silbert, S. K., Scanlon, S., Wang, H. W., Yuan, C. M., Doverte, A., Wellek, J., Patel, N., Braylan, R., Ahlman, M., Turkbey, E. B., Bohling, S. D., Chisholm, K. M., Oztek, M. A., Laloggia, M., Verma, A., Shalabi, H., Kovach, A. E., Wood, B. L., Lamble, A., ... Shah, N. N. (2024). CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy. Journal for immunotherapy of cancer, 12(10), Article e009499. https://doi.org/10.1136/jitc-2024-009499

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title = "CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy",

abstract = "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.",

keywords = "Chimeric antigen receptor - CAR, Immunotherapy, Leukemia, Next generation sequencing - NGS",

author = "Silbert, {Sara K.} and Samantha Scanlon and Wang, {Hao Wei} and Yuan, {Constance M.} and Alyssa Doverte and Jake Wellek and Nisha Patel and Raul Braylan and Mark Ahlman and Turkbey, {Evrim B.} and Bohling, {Sandra D.} and Chisholm, {Karen M.} and Oztek, {Murat Alp} and Mike Laloggia and Anupam Verma and Haneen Shalabi and Kovach, {Alexandra E.} and Wood, {Brent L.} and Adam Lamble and Ilan Kirsch and Kasey Leger and Shah, {Nirali N.}",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2024.",

year = "2024",

month = oct,

day = "26",

doi = "10.1136/jitc-2024-009499",

language = "English (US)",

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Silbert, SK, Scanlon, S , Wang, HW, Yuan, CM, Doverte, A, Wellek, J, Patel, N, Braylan, R, Ahlman, M, Turkbey, EB, Bohling, SD, Chisholm, KM, Oztek, MA, Laloggia, M, Verma, A, Shalabi, H, Kovach, AE, Wood, BL, Lamble, A, Kirsch, I, Leger, K & Shah, NN 2024, 'CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy', Journal for immunotherapy of cancer, vol. 12, no. 10, e009499. https://doi.org/10.1136/jitc-2024-009499

TY - JOUR

T1 - CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy

AU - Silbert, Sara K.

AU - Scanlon, Samantha

AU - Wang, Hao Wei

AU - Yuan, Constance M.

AU - Doverte, Alyssa

AU - Wellek, Jake

AU - Patel, Nisha

AU - Braylan, Raul

AU - Ahlman, Mark

AU - Turkbey, Evrim B.

AU - Bohling, Sandra D.

AU - Chisholm, Karen M.

AU - Oztek, Murat Alp

AU - Laloggia, Mike

AU - Verma, Anupam

AU - Shalabi, Haneen

AU - Kovach, Alexandra E.

AU - Wood, Brent L.

AU - Lamble, Adam

AU - Kirsch, Ilan

AU - Leger, Kasey

AU - Shah, Nirali N.

PY - 2024/10/26

Y1 - 2024/10/26

N2 - 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.

AB - 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.

KW - Chimeric antigen receptor - CAR

KW - Immunotherapy

KW - Leukemia

KW - Next generation sequencing - NGS

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U2 - 10.1136/jitc-2024-009499

DO - 10.1136/jitc-2024-009499

M3 - Article

C2 - 39461880

AN - SCOPUS:85207998878

SN - 2051-1426

VL - 12

JO - Journal for immunotherapy of cancer

JF - Journal for immunotherapy of cancer

IS - 10

M1 - e009499

ER -

CRLF2 -rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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