TY - JOUR
T1 - Leukocyte immunoglobulin-like receptor B1 and B4 (LILRB1 and LILRB4)
T2 - Highly sensitive and specific markers of acute myeloid leukemia with monocytic differentiation
AU - Churchill, Hywyn R.O.
AU - Fuda, Franklin S.
AU - Xu, Jing
AU - Deng, Mi
AU - Zhang, Cheng Cheng
AU - An, Zhiqiang
AU - Zhang, Ningyan
AU - Chen, Pu
AU - Bergstrom, Colin
AU - Kansagra, Ankit
AU - Collins, Robert
AU - John, Samuel
AU - Koduru, Prasad
AU - Chen, Weina
N1 - Publisher Copyright:
© 2020 International Clinical Cytometry Society
PY - 2021/7
Y1 - 2021/7
N2 - Background: Acute myeloid leukemia (AML) with monocytic differentiation (M-AML) remains a diagnostic challenge largely due to lack of sensitive and specific markers for immature monocytes. The immunoglobulin-like inhibitory receptors, LILRB1 and LILRB4, are expressed on monocytes but have not yet been systematically evaluated in the clinical setting. Methods: We evaluated the diagnostic performance of LILRB1 and LILRB4 as monocytic markers for both immature and mature monocytes in comparison to other myelomonocytic markers including CD14, CD15, CD33, CD36, and CD64 in eight cases of control bone marrow (BM, 5) and peripheral blood (PB, 3), 64 cases of (M-AML), and 57 cases of AML without monocytic differentiation (NM-AML) by flow cytometric immunophenotyping. Results: In control BM, LILRB1 and LILRB4 were consistently expressed on monocytes at all stages of maturation, from CD34+/CD14− monocytic precursors to CD14−/dim+ maturing and CD14+ mature monocytes. In M-AML, LILRB1 and LILRB4 were consistently expressed on monocytes, regardless of the degree of maturity, from CD14−/dim+ monoblasts/promonocytes to CD14+ mature monocytes but were not expressed on myeloblasts. The diagnostic performances as a monocytic marker assessed by sensitivity/specificity were 100%/100% for LILRB1/LILRB4, 100%/82% for CD11b, 80%/100% for CD14, 100%/81% for CD64, 100%/58% for CD15/CD33, and 89%/97% for CD36/CD64. Conclusion: The co-expression of LILRB1/LILRB4 outperformed other myelomonocytic markers as a highly sensitive and specific marker for monocytes at all stages of maturation and could reliably distinguish M-AML from NM-AML. LILRB4 additionally represents a novel therapeutic target for treating M-AML.
AB - Background: Acute myeloid leukemia (AML) with monocytic differentiation (M-AML) remains a diagnostic challenge largely due to lack of sensitive and specific markers for immature monocytes. The immunoglobulin-like inhibitory receptors, LILRB1 and LILRB4, are expressed on monocytes but have not yet been systematically evaluated in the clinical setting. Methods: We evaluated the diagnostic performance of LILRB1 and LILRB4 as monocytic markers for both immature and mature monocytes in comparison to other myelomonocytic markers including CD14, CD15, CD33, CD36, and CD64 in eight cases of control bone marrow (BM, 5) and peripheral blood (PB, 3), 64 cases of (M-AML), and 57 cases of AML without monocytic differentiation (NM-AML) by flow cytometric immunophenotyping. Results: In control BM, LILRB1 and LILRB4 were consistently expressed on monocytes at all stages of maturation, from CD34+/CD14− monocytic precursors to CD14−/dim+ maturing and CD14+ mature monocytes. In M-AML, LILRB1 and LILRB4 were consistently expressed on monocytes, regardless of the degree of maturity, from CD14−/dim+ monoblasts/promonocytes to CD14+ mature monocytes but were not expressed on myeloblasts. The diagnostic performances as a monocytic marker assessed by sensitivity/specificity were 100%/100% for LILRB1/LILRB4, 100%/82% for CD11b, 80%/100% for CD14, 100%/81% for CD64, 100%/58% for CD15/CD33, and 89%/97% for CD36/CD64. Conclusion: The co-expression of LILRB1/LILRB4 outperformed other myelomonocytic markers as a highly sensitive and specific marker for monocytes at all stages of maturation and could reliably distinguish M-AML from NM-AML. LILRB4 additionally represents a novel therapeutic target for treating M-AML.
KW - acute monocytic leukemia
KW - acute myeloid leukemia
KW - flow cytometry
KW - leukocyte immunoglobulin-like receptor B1 (LILRB1)
KW - leukocyte immunoglobulin-like receptor B4 (LILRB4)
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U2 - 10.1002/cyto.b.21952
DO - 10.1002/cyto.b.21952
M3 - Article
C2 - 32918786
AN - SCOPUS:85090765738
SN - 1552-4949
VL - 100
SP - 476
EP - 487
JO - Cytometry Part B - Clinical Cytometry
JF - Cytometry Part B - Clinical Cytometry
IS - 4
ER -