Adverse outcome of AML with aberrant CD16 and CD56 NK cell marker expression

Junge, Alexandra; Bacher, Ulrike; Mueller, Beatrice U.; Keller, Peter M.; Solenthaler, Max; Pabst, Thomas

doi:10.1002/hon.2516

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…Besides the well documented role of DNAM-1 in lymphocytes, expression was also reported for cells of the myeloid lineage like monocytes and platelets, where it mediates adhesion and migration 7 , 8 However, nothing is known regarding the expression and function of DNAM-1 on malignant cells of the myeloid lineage. Notably, aberrant expression of immune receptors normally found on NK cells was previously reported for AML cells, with the Fcɣ receptors CD32, CD64 and CD16 being prominent examples 9 – 12 .…”

Section: Introductionmentioning

confidence: 60%

DNAM-1/CD226 is functionally expressed on acute myeloid leukemia (AML) cells and is associated with favorable prognosis

Chashchina¹,

Märklin²,

Hinterleitner

et al. 2021

Sci Rep

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DNAM-1 is reportedly expressed on cytotoxic T and NK cells and, upon interaction with its ligands CD112 and CD155, plays an important role in tumor immunosurveillance. It has also been reported to be functionally expressed by myeloid cells, but expression and function on malignant cells of the myeloid lineage have not been studied so far. Here we analyzed expression of DNAM-1 in leukemic cells of acute myeloid leukemia (AML) patients. We found substantial levels of DNAM-1 to be expressed on leukemic blasts in 48 of 62 (> 75%) patients. Interaction of DNAM-1 with its ligands CD112 and CD155 induced release of the immunomodulatory cytokines IL-6, IL-8 IL-10 and TNF-α by AML cells and DNAM-1 expression correlated with a more differentiated phenotype. Multivariate analysis did not show any association of DNAM-1 positivity with established risk factors, but expression was significantly associated with clinical disease course: patients with high DNAM-1 surface levels had significantly longer progression-free and overall survival compared to DNAM-1low patients, independently whether patients had undergone allogenic stem cell transplantation or not. Together, our findings unravel a functional role of DNAM-1 in AML pathophysiology and identify DNAM-1 as a potential novel prognostic maker in AML.

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Section: Introductionmentioning

confidence: 60%

DNAM-1/CD226 is functionally expressed on acute myeloid leukemia (AML) cells and is associated with favorable prognosis

Chashchina¹,

Märklin²,

Hinterleitner

et al. 2021

Sci Rep

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“…In AML, aberrant expression of CD56 is found in 13%‐29% of cases 2 and expression levels can be heterogeneous across different disease subentities. Clinically CD56‐positive AML is characterized by a worse prognosis 1,3 and a higher incidence of extramedullary spread including infiltration of the central nervous system 4‐6 . Since CD56 plays an important function in neuronal growth and migration through cell to cell adhesion, it is hypothesized that CD56 expression on leukemic blast cells could mediate tissue infiltration by blasts through adhesion to other cells that also express CD56 4,7 .…”

Section: Introductionmentioning

confidence: 99%

Blast counts are lower in the aspirate as compared to trephine biopsy in acute myeloid leukemia and myelodysplastic syndrome expressing CD56

Drexler

Tzankov

Martínez

et al. 2021

Int J Lab Hematology

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Introduction CD56 is aberrantly expressed in myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Considering the adhesion effects of CD56, blast quantification in bone marrow might depend on the technique used to obtain respective diagnostic specimens. Therefore, the objective of our study was to investigate the impact of CD56‐expression on blast counts in myeloid neoplasms comparing bone marrow aspirates to biopsies. Methods We retrospectively analyzed 75 patients diagnosed with MDS and AML. We compared patients with (n = 36) and without (n = 39) CD56‐expression by flow cytometry with respect to their blast quantities assessed on bone marrow aspirates versus biopsies. Results The frequency of CD56‐expression on blasts correlated with higher blast counts on biopsies vs. aspirate smears (rs = 0.52; P = .001). This difference in blast counts was only significant in the CD56 high expressing subgroup (median 68%, 5.5%‐95% in biopsy compared to median 32.5%, 1.5%‐90% in aspirate; P < .01). The percentage of CD56‐positive blasts among the total blast population was lower in the peripheral blood compared to bone marrow (median 31%, 6%‐88% vs. 55%, 14%‐98%; P = .016). The discrepancy in the blast count between the aspirate and trephine biopsy would have led to misclassification of four cases as MDS instead of AML, if diagnosis had based on the bone marrow aspirate blast count alone. Conclusion Counting blasts in bone marrow aspirates of CD56‐positive AML and MDS may be linked to underestimation, potentially leading to misclassification of these myeloid neoplasms, and should therefore be adjusted considering the results obtained on trephine biopsies for reliable diagnosis.

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“…Prognosis is related not only to age, sex, karyotype, white blood cell (WBCs) count and blast cell count but also to the expression and mutation of some critical genes (6). Several biomarkers have been proven to be useful in the diagnosis and prognosis of AML according to recent studies (7,8) and some reports have shown that the expression levels of some genes, such as SETBP1, VEGFC and EVI1, are associated with the risk level and the survival of patients (9)(10)(11). However, OS and DFS of patients with AML remain poor (12,13).…”

Section: Introductionmentioning

confidence: 99%

Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

et al. 2020

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Acute myeloid leukemia (AML) is a hematological malignancy with a poorly understood pathogenesis, especially among patients with no known cytogenetic abnormalities. Furthermore, there is a lack of therapeutic gene targets and diagnostic biomarkers for the effective treatment of AML. The present study aimed to identify candidate biomarkers correlated with the clinical prognosis of patients with AML. Leukemic cells from 5 patients with AML exhibiting a normal karyotype, and hematopoietic cells from 5 healthy donors were processed for RNA sequencing (RNA-seq), and the obtained RNA expression profiles were subjected to weighted gene correlation network analysis. A novel group of genes (the red module) were identified to be significantly associated with AML, and this module contained a closely connected network with 147 nodes, which corresponded to 114 mRNAs. Analysis of the correlation between these mRNAs and blast cell percentage, overall survival (OS) and disease-free survival (DFS) using cases from The Cancer Genome Atlas (TCGA) database revealed that CSF3R, ALPL and LMTK2 were negatively associated with the percentage of blast cells, while high expression of these genes was associated with longer OS and DFS in patients with AML. The differential expression of these three genes between patients with AML and healthy control subjects was supported using the Genotype-Tissue Expression and TCGA databases and was further confirmed using reverse transcription-quantitative (RT-qPCR). These genes exhibited significantly lower expression in patients with AML compared with control subjects. The results indicated that CSF3R, ALPL and LMTK2 exhibit the potential to be prognostic biomarkers. However, the biological functions of these three candidate genes need to be assessed in further studies.

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Adverse outcome of AML with aberrant CD16 and CD56 NK cell marker expression

Cited by 10 publications

References 40 publications

DNAM-1/CD226 is functionally expressed on acute myeloid leukemia (AML) cells and is associated with favorable prognosis

DNAM-1/CD226 is functionally expressed on acute myeloid leukemia (AML) cells and is associated with favorable prognosis

Blast counts are lower in the aspirate as compared to trephine biopsy in acute myeloid leukemia and myelodysplastic syndrome expressing CD56

Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

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