New Hope for the Diagnosis of M-AML: CD85j and CD85k

M-AML

In the field of diagnosis of hematological diseases, the diagnosis of acute myeloid leukemia with monocytic differentiation (M-AML) has always been a thorny problem. Due to the lack of sensitive and specific markers for immature monocytes, doctors often face challenges in diagnosing this type of disease and find it difficult to make accurate judgments. However, with the continuous advancement of medical research, Hywyn R O Churchill and his colleagues from the Department of Pathology, University of Texas Southwestern Medical Center, USA, have brought exciting news. They have discovered two markers with extremely high sensitivity and specificity in the diagnosis of M-AML, namely CD85j (LILRB1) and CD85k (LILRB4).

CD85j and CD85k

The CD85 family belongs to the immunoglobulin (Ig) superfamily of transmembrane glycoproteins. Among them, CD85j and CD85k have their own unique structures and functions. CD85j is a 110kD member, also known as ILT2, LIR1, etc. Its structure contains four Ig domains, and the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic tail can recruit Src homology region 2 domain-containing phosphatase-1 (SHP-1) to provide inhibitory signals. It is widely present on the surface of various immune cells. CD85k, namely ILT3, is an inhibitory receptor expressed on dendritic cells and monocytes. It belongs to type I membrane proteins and contains cytoplasmic ITIM groups, playing an important role in the downregulation of immune responses. Previously, although it was known that these two proteins were expressed on monocytes, their value in clinical diagnosis had not been systematically evaluated.

Research Findings

In order to explore the performance of CD85j and CD85k in the diagnosis of M-AML, the Churchill team conducted a study. They selected 8 control bone marrow and peripheral blood samples, as well as 64 M-AML samples and 57 AML samples without monocytic differentiation (NM-AML). Using flow cytometric immunophenotyping technology, they evaluated CD85j (LILRB1), CD85k (LILRB4), and other myeloid markers such as CD14, CD15, and CD33. The results were surprising: in the control bone marrow, both CD85j and CD85k were expressed at all stages of monocytes, from CD34+/CD14- monocyte precursors to mature monocytes; in M-AML samples, these two markers were continuously expressed on monocytes regardless of their maturity, but not expressed on promyelocytes. More importantly, in terms of the sensitivity/specificity data of diagnostic performance, the combination of CD85j/CD85k reached 100%/100%, significantly superior to other common bone marrow cell markers such as CD11b, CD14, and CD64. This means that the co-expression of CD85j and CD85k can reliably distinguish M-AML from NM-AML, providing an extremely accurate basis for clinical diagnosis.

CD85k

The value of CD85k (LILRB4) is not limited to this. It is highly likely to become a new target for the treatment of M-AML. Currently, CD85k has been applied in many places, but people may not fully recognize its high sensitivity and specificity. In the future, it is necessary for various medical centers to further summarize the data and explore whether there are differences in the performance of these two markers among different regions and different patient groups, so as to better apply them to clinical practice.

Conclusion

The research findings on CD85j and CD85k this time have opened up a new direction for the diagnosis and treatment of M-AML. It is believed that with the in-depth development of subsequent research and the accumulation of more clinical data, these two markers will play a greater role in the field of hematological diseases, bring more hope to patients, and promote the development of precision medicine in hematological diseases.