Primary cytotoxic T-cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway

Katie Lee; Mark G Evans; Lei Yang; Spencer Ng; Caroline Snowden; Michael Khodadoust; Ryanne A Brown; Nicholas A Trum; Christiane Querfeld; Linda T Doan; Jinming Song; Hailing Zhang; Alejandro A Gru; Gary S Wood; David A Wada; Vignesh Shanmugam; Paul L Haun; Jon C Aster; Lyn M Duncan; Joan Guitart; David M Weinstock; Valentina Nardi; Jaehyuk Choi

doi:10.1182/blood.2021012536

Primary cytotoxic T-cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway

Blood. 2021 Dec 9;138(23):2435-2440. doi: 10.1182/blood.2021012536.

Authors

Katie Lee^{1

2}, Mark G Evans³, Lei Yang⁴, Spencer Ng¹, Caroline Snowden^{1

2}, Michael Khodadoust^{5

1}, Ryanne A Brown^{1

6}, Nicholas A Trum⁷, Christiane Querfeld⁷, Linda T Doan⁸, Jinming Song⁹, Hailing Zhang⁹, Alejandro A Gru¹⁰, Gary S Wood¹¹, David A Wada^{1

12}, Vignesh Shanmugam³, Paul L Haun¹³, Jon C Aster³, Lyn M Duncan¹⁴, Joan Guitart¹, David M Weinstock⁴, Valentina Nardi¹⁴, Jaehyuk Choi^{1

2

15

16}

Affiliations

¹ Department of Dermatology and.
² Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL.
³ Department of Pathology, Brigham and Women's Hospital and.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
⁵ Division of Oncology, Department of Medicine.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA.
⁷ Department of Dermatology, City of Hope National Medical Center, Duarte, CA.
⁸ Department of Dermatology, University of California, Irvine, Irvine, CA.
⁹ Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
¹⁰ Department of Pathology, University of Virginia, Charlottesville, VA.
¹¹ Department of Dermatology, University of Wisconsin, Madison, WI.
¹² Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT.
¹³ Penn Cutaneous Lymphoma Program, Department of Dermatology, Perelman Center for Advanced Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
¹⁴ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹⁵ Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; and.
¹⁶ Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

Abstract

Primary cytotoxic T cell lymphomas (CTCLs) are a rare subset of aggressive, poor-prognosis T-cell lymphomas targeting the skin; they include primary cutaneous γδT-cell lymphoma, primary cutaneous VD8⁺ aggressive epidermotropic T cell lymphoma (PCAETCL), and cytotoxic CTCL not otherwise specified. Lee et al report that all 3 subsets have JAK-STAT activation, but PCAETCL uniquely carries JAK2 gene fusions that may render them especially susceptible to JAK inhibitors.

Publication types

Letter
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Humans
Janus Kinases / genetics
Janus Kinases / metabolism*
Lymphoma, T-Cell / drug therapy
Lymphoma, T-Cell / genetics
Lymphoma, T-Cell / metabolism*
Molecular Targeted Therapy
Mutation / drug effects
STAT Transcription Factors / genetics
STAT Transcription Factors / metabolism*
Signal Transduction* / drug effects

Substances

Antineoplastic Agents
STAT Transcription Factors
Janus Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding