Universal monitoring of minimal residual disease in acute myeloid leukemia

Coustan‐Smith, Elaine; Song, Guangchun; Shurtleff, Sheila; Yeoh, Allen Eng Juh; Chng, Wee Joo; Chen, Siew Peng; Rubnitz, Jeffrey E.; Pui, Ching‐Hon; Downing, James R.; Campana, Dario

doi:10.1172/jci.insight.98561

Cited by 68 publications

(57 citation statements)

References 57 publications

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“…These findings are particularly relevant as the majority of antigens associated with LSCs (ie, TIM3, CLL1, and CD244) are less expressed on these cells compared to bulk cells and are frequently coexpressed on normal HSCs and progenitors . Recently, Coustan‐Smith et al published a study on MRD monitoring in AML by MFC and, interestingly, they found an overexpression of CD9 on blast cells (in 30% of AML cases) compared to physiologic myeloblasts . Furthermore, they showed that CD9 was abnormally overexpressed on CD34+CD38− AML cells at diagnosis and relapse of 10 paired samples, thus corroborating the MFC strategy on LSCs that we used in this study.…”

Section: Discussionmentioning

confidence: 99%

CD9 in acute myeloid leukemia: Prognostic role and usefulness to target leukemic stem cells

et al. 2019

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CD9 is a cell surface protein and belongs to the tetraspanin family. Its role in carcinomagenesis has been widely studied in solid tumors but remains controversial, depending on the cancer type. Although CD9 seems to be associated with unfavorable outcome and disease progression in acute lymphoblastic leukemia (ALL), this marker has not yet been studied in acute myeloid leukemia (AML). First, we explored its prognostic role and its association with biological factors in a cohort of 112 AML patients treated with intensive chemotherapy. CD9 was expressed in 40% of AML and was associated with a favorable outcome (event‐free survival and relapse‐free survival) in univariate (P = 0.009 and P = 0.048, respectively) and multivariate (P = 0.004 and P = 0.039, respectively) analyses. Interestingly, CD9 expression was different between the more immature physiologic and AML cells (CD34+CD38−) as it was also expressed in AML on putative leukemic stem cells (LSCs) but not on hematopoietic stem cells (HSCs). Hence, CD9 could be a very relevant marker for minimal residual disease (MRD) monitoring in AML based on LSC targeting.

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Section: Discussionmentioning

confidence: 99%

CD9 in acute myeloid leukemia: Prognostic role and usefulness to target leukemic stem cells

et al. 2019

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“…150 However, more studies are needed to corroborate these results, particularly since other researchers have reported the upregulated expression of hCD96 on cells within the tumor microenvironment and hCD96 itself was identified as tumor marker. [87][88][89]151 Finally, although CD96 was originally identified as a human T cell antigen, 86 its function in T cells generally remains obscure, particularly in the field of tumor immunology. Hence, in addition to critical points regarding the inhibitory potential of hCD96, many other unresolved questions remain on this subject.…”

Section: Recombinant Oncolytic Poliovirusesmentioning

confidence: 99%

Targeting PVR (CD155) and its receptors in anti-tumor therapy

Brlić

Roviš

Cinamon³

et al. 2018

Cell Mol Immunol

126

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Poliovirus receptor (PVR, CD155) has recently been gaining scientific interest as a therapeutic target in the field of tumor immunology due to its prominent endogenous and immune functions. In contrast to healthy tissues, PVR is expressed at high levels in several human malignancies and seems to have protumorigenic and therapeutically attractive properties that are currently being investigated in the field of recombinant oncolytic virotherapy. More intriguingly, PVR participates in a considerable number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors. These functions are often modified in the tumor microenvironment, contributing to tumor immunosuppression. Indeed, increasing evidence supports the rationale for developing strategies targeting these interactions, either in terms of checkpoint therapy (i.e., targeting inhibitory receptors) or in adoptive cell therapy, which targets PVR as a tumor marker.

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“…The poor sensitivity limits the diagnostic utility of CSF cytology. And leukemic cells become undetectable after chemotherapy in most patients with AML [28]. Several previous reports have demonstrated that the sensitivity of ow cytometry is superior to conventional cytology for the early identi cation of CSF in ltration by leukemia or lymphoma cells, but due to the limited number of antibodies, its weak capacity to provide de nite diagnostic clues needs to be improved (most likely due to small sample size and the small number of cells).…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Cerebrospinal Fluid Beta2-microglobulin and Prognosis of Patients with Acute Myeloid Leukemia Subtype M2 After Chemotherapy

Yao

Shi

Zhou

et al. 2020

Preprint

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Background: The correlation of cerebrospinal fluid beta2-microglobulin (CSF-β2MG) and prognosis of acute myeloid leukemia subtype M2 (AML-M2) receiving chemotherapy is uncertain. We seek to explore the prognostic and predictive value of CSF-β2MG in AML-M2 receiving chemotherapy.Methods: CSF-β2MG levels were detected by immunoturbidimetry in a cohort comprised of 40 AML-M2 patients, 25 of whom were categorized into the effective chemotherapy group (Complete Remission (CR) & Partial Remission (PR) and 15 patients into the ineffective group (Non-response (NR) & Death). The correlations between changes (%) in CSF-β2MG from baseline (change between the pre- and post-chemotherapy) or CSF-β2MG (the absolute levels of post-chemotherapy) and prognosis classifications of AML-M2 were assessed. The best cut-off points were investigated.Results: Levels of CSF-β2MG after chemotherapy and percentage change from baseline was variably presented among AML-M2s and progressively more advanced CSF-β2MG levels were associated with worse prognosis and poor therapeutic outcomes. The optimal cut-off value had the potential to be a predictor of treatment failure, hence the value for auxiliary diagnosis and accurate management.Conclusions: Changes in CSF-β2MG could be used to predict clinical outcomes of chemotherapy in patients with AML-M2. The association between changes in CSF-β2MG and the efficacy of chemotherapy thus becomes clearer but requires further study.

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Universal monitoring of minimal residual disease in acute myeloid leukemia

Cited by 68 publications

References 57 publications

CD9 in acute myeloid leukemia: Prognostic role and usefulness to target leukemic stem cells

CD9 in acute myeloid leukemia: Prognostic role and usefulness to target leukemic stem cells

Targeting PVR (CD155) and its receptors in anti-tumor therapy

Correlation Between Cerebrospinal Fluid Beta2-microglobulin and Prognosis of Patients with Acute Myeloid Leukemia Subtype M2 After Chemotherapy

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