TY - JOUR
T1 - LILRB4 expression in chronic myelomonocytic leukemia and myelodysplastic syndrome based on response to hypomethylating agents
AU - Chien, Kelly S.
AU - Class, Caleb A.
AU - Montalban-Bravo, Guillermo
AU - Wei, Yue
AU - Sasaki, Koji
AU - Naqvi, Kiran
AU - Ganan-Gomez, Irene
AU - Yang, Hui
AU - Soltysiak, Kelly A.
AU - Kanagal-Shamanna, Rashmi
AU - Do, Kim Anh
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/5/11
Y1 - 2020/5/11
N2 - LILRB4 is expressed in AML M4/M5 cells and negatively regulates immune cell activation via T-cell suppression. Its expression and role in chronic myelomonocytic leukemia (CMML) and myelodysplastic syndrome (MDS) are unknown. We investigated LILRB4 expression in 19 CMML and 27 MDS patients and correlated it with response to subsequent hypomethylating agent (HMA) therapy. LILRB4 RNA expression was increased in CMML patients when compared to MDS patients and healthy controls (q < 0.1) and slightly increased in patients who responded to HMAs (q > 0.1). Pathway analysis revealed upregulation of PD-1 signaling, CTLA-4 signaling, and inflammatory response, and gene correlates were positively associated with CTLA-4 expression. Given current modest results with immunotherapy in myeloid malignancies, further investigation of LILRB4 as an immune checkpoint inhibitor target is needed. With the positive correlation between LILRB4 and CTLA-4 expression, combining anti-LILRB4 and anti-CTLA-4 agents may be a novel therapeutic approach in myeloid malignancies that warrants larger studies.
AB - LILRB4 is expressed in AML M4/M5 cells and negatively regulates immune cell activation via T-cell suppression. Its expression and role in chronic myelomonocytic leukemia (CMML) and myelodysplastic syndrome (MDS) are unknown. We investigated LILRB4 expression in 19 CMML and 27 MDS patients and correlated it with response to subsequent hypomethylating agent (HMA) therapy. LILRB4 RNA expression was increased in CMML patients when compared to MDS patients and healthy controls (q < 0.1) and slightly increased in patients who responded to HMAs (q > 0.1). Pathway analysis revealed upregulation of PD-1 signaling, CTLA-4 signaling, and inflammatory response, and gene correlates were positively associated with CTLA-4 expression. Given current modest results with immunotherapy in myeloid malignancies, further investigation of LILRB4 as an immune checkpoint inhibitor target is needed. With the positive correlation between LILRB4 and CTLA-4 expression, combining anti-LILRB4 and anti-CTLA-4 agents may be a novel therapeutic approach in myeloid malignancies that warrants larger studies.
KW - LILRB4
KW - Myelodysplastic syndromes
KW - chronic myelomonocytic leukemia
KW - hypomethylating agents
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U2 - 10.1080/10428194.2020.1723014
DO - 10.1080/10428194.2020.1723014
M3 - Article
C2 - 32036728
AN - SCOPUS:85079237683
SN - 1042-8194
VL - 61
SP - 1493
EP - 1499
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 6
ER -