STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL

J Jason Xu J Jonathan H. Sussman A Austin Yang (7Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA) S Satoshi Yoshimura (Department of Pharmacy and Pharmaceutical Sciences) J Jianzhong Hu C Changya Chen (2Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China) T Tiffaney Vincent (3Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA) S Shovik Bandyopadhyay (2Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) E Elizabeth Y. Li (3Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA) T Tristan Lim (7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) O Omar Elghawy (2Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA) A Adam Barsouk (2Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA) D Damjan Karanfilovski (7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) S Shira L. Wald (7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) G Gregory M. Chen (1Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) D David Wu H Haley Newman (1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States) A Alexander Li (Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States) Y Yusha Sun C Chia-Hui Chen (5Children's Hospital of Philadelphia, Center for Childhood Cancer Research, Philadelphia, United States) K Kathrin Bernt (1Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Oncology, Philadelphia, United States) B Brent L. Wood (Department of Pathology and Laboratory Medicine, Children’s Hospital of Los Angeles, Los Angeles) S Stuart S. Winter (11Division of Hematology Oncology, Children's Minnesota, Eagan, MN) K Kimberly P. Dunsmore (12Division of Oncology, University of Virginia Health Sciences Center, Charlottesville, VA) E Elizabeth Raetz (11NYU Langone Health, New York, United States) M Meenakshi Devidas (Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN) S Stanley Pounds M Mignon Loh (13Ben Towne Center for Childhood Cancer Research and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA) S Stephen P. Hunger (Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia) M Mark Y. Chiang (16Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI) C Caroline Diorio D Danika Di Giacomo (1Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN) P Petri Pölönen C Charles G. Mullighan J Jun J. Yang (Department of Pharmacy and Pharmaceutical Sciences) K Kai Tan D David T. Teachey

Abstract

Abstract We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children’s Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.

Article Details

Journal Blood
Volume / Issue Vol. 145, Issue 23
Published June 05, 2025
Pages 2793-2798
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (37)

J

Jason Xu

J

Jonathan H. Sussman

A

Austin Yang

7Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA

S

Satoshi Yoshimura

Department of Pharmacy and Pharmaceutical Sciences

J

Jianzhong Hu

C

Changya Chen

2Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

T

Tiffaney Vincent

3Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA

S

Shovik Bandyopadhyay

2Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

E

Elizabeth Y. Li

3Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA

T

Tristan Lim

7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

O

Omar Elghawy

2Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA

A

Adam Barsouk

2Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA

D

Damjan Karanfilovski

7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

S

Shira L. Wald

7Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

G

Gregory M. Chen

1Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

D

David Wu

H

Haley Newman

1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States

A

Alexander Li

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States

Y

Yusha Sun

C

Chia-Hui Chen

5Children's Hospital of Philadelphia, Center for Childhood Cancer Research, Philadelphia, United States

K

Kathrin Bernt

1Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Oncology, Philadelphia, United States

B

Brent L. Wood

Department of Pathology and Laboratory Medicine, Children’s Hospital of Los Angeles, Los Angeles

S

Stuart S. Winter

11Division of Hematology Oncology, Children's Minnesota, Eagan, MN

K

Kimberly P. Dunsmore

12Division of Oncology, University of Virginia Health Sciences Center, Charlottesville, VA

E

Elizabeth Raetz

11NYU Langone Health, New York, United States

M

Meenakshi Devidas

Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN

S

Stanley Pounds

M

Mignon Loh

13Ben Towne Center for Childhood Cancer Research and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA

S

Stephen P. Hunger

Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia

M

Mark Y. Chiang

16Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI

C

Caroline Diorio

D

Danika Di Giacomo

1Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN

P

Petri Pölönen

C

Charles G. Mullighan

J

Jun J. Yang

Department of Pharmacy and Pharmaceutical Sciences

K

Kai Tan

D

David T. Teachey